The Week 6 NFL schedule for the 2023 season is stacked with great matchups, and we have you covered with what you need to know heading into the weekend. Our NFL Nation reporters bring us the biggest keys to every game and a bold prediction for each matchup.
Additionally, ESPN Stats & Information provides a big stat to know and a betting nugget for each contest, and our Football Power Index (FPI) goes inside the numbers with a game projection. Analytics writer Seth Walder picks out each matchup’s biggest X factor, and fantasy analyst Eric Moody hands out helpful fantasy football intel. Finally, Walder and Moody give us final score picks for every game. Everything you want to know is here in one spot to help you get ready for a loaded weekend of NFL football.
Let’s get into the full Week 6 slate, including a Ravens-Titans showdown in London, a Belichick-McDaniels reunion in Vegas and an NFC North matchup between the Vikings and Bears. It all culminates with a “Monday Night Football” matchup between the Cowboys and Chargers on ESPN. (Game times are Sunday unless otherwise noted.)
9:30 a.m. ET | NFL Network | Spread: BAL -4 (41)
Storyline to watch: The Titans have scored touchdowns on only 35.3% of their red zone visits this season, landing them in a tie with the Texans for third worst in the NFL. Meanwhile, the Ravens’ red zone defense has given up touchdowns on an NFL-low 25% of opposing offenses’ visits inside the 20-yard line. Getting seven points instead of kicking field goals could be the difference, as three of the Titans’ five games this season have been decided by one score. — Turron Davenport
Bold prediction: Zay Flowers will score his first career TD. The Ravens rookie receiver is certainly due; Flowers is tied with Jaguars tight end Evan Engram for the most catches this season (29) without reaching the end zone. But the Titans’ secondary has been good, giving up just five passing touchdowns so far. — Jamison Hensley
Stat to know: The Titans have scored fewer than 30 points in 23 straight games, the longest active streak in the NFL and the longest in franchise history.
Matchup X factor: Titans defensive lineman Denico Autry. When lined up as an edge rusher, Autry has a 24% pass rush win rate, which would rank right on the fringe of the top 10 if he qualified. And he has four sacks. Autry has the potential to disrupt the Baltimore pass game. — Walder
What to know for fantasy: Titans cornerback Kristian Fulton has given up 267 yards this season. Josh Downs, Ja’Marr Chase, Michael Pittman Jr. and others have exploited this matchup all season. Jackson and Flowers should do the same. See Week 6 rankings. — Moody
Betting nugget: Both teams have had four of their first five games this season go under the total, including three straight. Read more.
Moody’s pick: Ravens 28, Titans 23
Walder’s pick: Ravens 24, Titans 20
FPI prediction: BAL, 68.7% (by an average of 6.7 points)
Matchup must-reads: Beckham says ankle better, but he has to improve … Titans sticking to same routine as 2018 in search of first win in London … Ravens receivers will ‘be better’ after 5-drop game … Titans’ Fulton on penalties: Hard to play against refs and WRs
1 p.m. ET | FOX | Spread: SF -6.5 (37)
Storyline to watch: This game pits one of the NFL’s best offenses against one of its best defenses. The 49ers are No. 2 in offensive efficiency (87.1), while the Browns are No. 1 in defensive (87.0). The 49ers have scored 30 points in eight straight games, the fifth-longest streak in NFL history — but the Browns have given up just five offensive touchdowns all season. — Jake Trotter
Bold prediction: 49ers defensive end Nick Bosa will get three sacks. Despite getting consistent pressure, Bosa has just 1.5 sacks through the first five games. But there’s reason to believe a breakout is coming. Browns quarterbacks are averaging 3.09 seconds to throw, the second-slowest average in the league. Most teams emphasize getting the ball out quick against the Niners, but that hasn’t been a strength of Cleveland. Regardless who starts at QB for the Browns, Bosa can get his sack total back on track here. — Nick Wagoner
Stat to know: This will be Cleveland defensive end Myles Garrett‘s 89th career game. His 80 sacks are the third most by any player in his first 90 career games since 1982, when sacks became official, after Hall of Famer Reggie White (98) and the Steelers’ T.J. Watt (83.5).
Matchup X factor: 49ers offensive tackle Trent Williams. One of the only ways the Browns can win this game is if Garrett takes over — which he can. But fortunately for the Niners, Garrett typically lines up against the left tackle, and that’s where the strength of their offensive line lies. — Walder
What to know for fantasy: San Francisco allows the eighth-fewest fantasy points per game to running backs. Managers who are thinking of starting Jerome Ford should consider other options. See Week 6 rankings. — Moody
Betting nugget: The 49ers are 4-0-1 against the spread (ATS) this season with three straight covers. They are the only team left without an ATS loss. Read more.
Moody’s pick: 49ers 28, Browns 14
Walder’s pick: 49ers 23, Browns 17
FPI prediction: SF, 66.2% (by an average of 5.8 points)
Matchup must-reads: 49ers receivers must clear out defenders before catching passes … How Jim Schwartz has transformed the Browns’ defense … 49ers send strong statement to NFL with domination of Cowboys
Kittle on 49ers’ hot start: We wanted to hit the ground running this season
George Kittle joins Pat McAfee to break down the team’s motivation going into this season after their loss to the Eagles in the NFC Championship game.
1 p.m. ET | CBS | Spread: CIN -2.5 (45)
Storyline to watch: This game will be determined by how well Bengals QB Joe Burrow and the offense respond to Seahawks’ pass rush. Seattle ranks fourth in the NFL in pass rush win rate (55%), and its defensive front has the Bengals’ full attention. That group will be a great test for Burrow’s mobility as he continues to improve from his calf injury. — Ben Baby
Bold prediction: The Seahawks will blitz Burrow early and often. When pressured this season, Burrow ranks near the bottom of the NFL in yards per attempt (3.1, 31st), completion percentage (36.4%, 26th) and QBR (10.7, 24th). That’s likely a product of his injured calf, though it didn’t seem to affect him as much last week. With Jamal Adams back from his concussion, the Seahawks — coming off their 11-sack performance against the Giants — will come after Burrow until he proves he can beat their blitzes with his arm and/or legs. — Brady Henderson
Stat to know: The Bengals have won six straight regular-season games against NFC opponents, the second-longest active win streak vs. the opposing conference. (The Eagles have won eight straight vs. the AFC).
Matchup X factor: Seahawks cornerbacks Riq Woolen and Michael Jackson. The reemergence of the Burrow-Ja’Marr Chase connection last week makes the Bengals dangerous again. But if the Seahawks’ corners can slow down Chase, the Bengals’ offense could scuffle with Tee Higgins questionable to play. — Walder
What to know for fantasy: The Seahawks’ defense has allowed the second-most fantasy points per game to wide receivers. It is a good sign for fantasy managers who have Burrow, Chase or another Bengals pass-catcher on their team. See Week 6 rankings. — Moody
Betting nugget: The Seahawks have covered in three straight games. Read more.
Moody’s pick: Bengals 30, Seahawks 20
Walder’s pick: Seahawks 29, Bengals 21
FPI prediction: SEA, 53.5% (by an average of 1.3 points)
1 p.m. ET | FOX | Spread: MIN -2.5 (44.5)
Storyline to watch: Two wide receivers are in the spotlight for this NFC North showdown for contrasting reasons. The Vikings will be without Justin Jefferson after a hamstring injury landed him on injured reserve, while Chicago’s DJ Moore is coming off a performance against Washington that earned him NFC Offensive Player of the Week (230 receiving yards, three touchdowns). Jefferson and Moore rank third (571) and fifth (531), respectively, among all players in receiving yards entering Week 6. — Courtney Cronin
Bold prediction: Justin Fields will have more passing yards than Kirk Cousins. Fields has thrown for 617 yards in his past two games, the fourth most in the NFL over that stretch. Cousins has the NFL’s second-most passing yards this season (1,498), but the Vikings are certain to dial back their passing game in the absence of Jefferson. — Kevin Seifert
Stat to know: The Vikings are 1-4 this season in one-score games (11-0 last season). They are the only team to play in five one-score games in 2023.
Matchup X factor: Moore. He’s an offseason acquisition who appears to be working out. In addition to recording more than 500 yards in five games, Moore leads all wide receivers and tight ends in the Receiver Tracking Metrics‘ Overall Score (85) — which measures receivers’ abilities to get open, make the catch and generate yards after the catch, all relative to expectation. — Walder
What to know for fantasy: The Bears’ defense gives up the third-most fantasy points per game to running backs. The Vikings should see neutral to positive game flow against Chicago, which bodes well for Alexander Mattison‘s fantasy outlook. In four of his five games this season, he has scored 10 or more fantasy points. See Week 6 rankings. — Moody
Betting nugget: All five Bears games have gone over the total this season. Vikings games are 4-1 to the over with three straight overs. Read more.
Moody’s pick: Bears 28, Vikings 24
Walder’s pick: Vikings 34, Bears 20
FPI prediction: MIN, 59.6% (by an average of 3.4 points)
Why Matt Bowen sees DJ Moore as a WR1 in Week 6
Matt Bowen explains why DJ Moore should be started in all fantasy lineups in Week 6.
1 p.m. ET | CBS | Spread: ATL -2.5 (42.5)
Storyline to watch: This will once again be an incredibly close game — and history proves it. The Falcons and Commanders played in 2021 (Washington won with 33 seconds left) and in 2022 (Marcus Mariota threw an interception in the Washington end zone with 1:03 remaining), with Washington winning both times. The big key will be on the lines, where Washington’s talented defensive front will try to cause havoc for Atlanta quarterback Desmond Ridder, who has been sacked 16 times in five games. — Michael Rothstein
Bold prediction: Washington defensive end Chase Young will force a fumble or interception by Ridder. Young has three sacks in his four games and was highly active in the loss to Chicago in Week 4, with a pass rush win rate of 36.4%. — John Keim
Stat to know: Washington quarterback Sam Howell has been sacked an NFL-high 29 times this season. David Carr (39 in 2002) is the most-sacked quarterback through a team’s first six games of a season since sacks were first tracked in 1963.
Matchup X factor: The Commanders’ pass rush. Despite having big names, the Commanders rank just 26th in pass rush win rate. Ridder has taken sacks at a higher-than-average 9% rate, so this is a big opportunity to get the unit going. — Walder
What to know for fantasy: Managers should temper expectations when it comes to skill position players on the Commanders. The Falcons’ defense is allowing only 3.8 yards per rushing attempt to opposing running backs. Atlanta’s defense also does a great job containing wide receivers, giving up the sixth-fewest fantasy points per game to the position. See Week 6 rankings. — Moody
Betting nugget: The Falcons are 0-4 ATS in their past four games. Read more.
Moody’s pick: Falcons 23, Commanders 19
Walder’s pick: Falcons 19, Commanders 16
FPI prediction: ATL, 58% (by an average of 2.8 points)
1 p.m. ET | CBS | Spread: MIA -13.5 (48.5)
Storyline to watch: Despite their 0-5 record, the Panthers’ aggressive defense has found some success this season in getting after opposing quarterbacks. Carolina has the fourth-highest sack rate in the NFL, coupled with the second-best third-down defense (29.8%). However, the Panthers also own by far the league’s worst expected points allowed (EPA) when defending the run (minus-14.4) and will face a Dolphins offense that ranks second in EPA per rush (16.8). — Marcel Louis-Jacques
Bold prediction: The Dolphins won’t top the 70 points they had earlier this year against Denver — but will top 50. The Carolina defense could be without two of its secondary starters and possibly three if cornerback Donte Jackson has a setback. Miami will get some help from its defense with a touchdown against a Panthers offense that surrendered 21 points off turnovers last week in a 42-24 loss to the Lions. — David Newton
Stat to know: The Dolphins have 2,568 total yards of offense this season, the most through five games in NFL history. Miami needs 489 more Sunday to pass the 2000 Rams (3,056) for most yards through six games.
Matchup X factor: Extreme unforeseen events. I’m trying to imagine which player is going to swing this game and, well, it’s going to take more than that. Wild weather? Bizarre fumble luck? Tua Tagovailoa waking up on the wrong side of the bed? The Panthers might need all three. — Walder
What to know for fantasy: Over the past four games, Panthers receiver Adam Thielen has averaged 11 targets. In three of those four games, he scored 20 or more fantasy points. Thielen should be busy against the Dolphins in a matchup the Panthers are likely to be playing from behind. See Week 6 rankings. — Moody
Betting nugget: The Panthers are 0-4-1 ATS this season. Read more.
Moody’s pick: Dolphins 42, Panthers 23
Walder’s pick: Dolphins 29, Panthers 12
FPI prediction: MIA, 87.6% (by an average of 15.8 points)
Is the pressure already on Bryce Young to succeed?
Chuck Pagano, Pat McAfee and A.J. Hawk discuss Bryce Young’s struggles early in his NFL career.
1 p.m. ET | CBS | Spread: JAX -4 (45.5)
Storyline to watch: Minshew Mania returns to its birthplace. Colts quarterback Gardner Minshew spent his first two seasons with the Jaguars and went 7-13 as a starter in 2019-20 before the team drafted Trevor Lawrence No. 1 overall in 2021. The bigger return, however, is Indy running back Jonathan Taylor to a larger role. He has rushed for 522 yards and three touchdowns in five games against the Jaguars. The Jaguars’ defense has been very good against the run so far, allowing 81.6 yards per game (ranked fifth in the NFL). That’s the matchup that will determine the outcome. — Mike DiRocco
Bold prediction: The Colts will rush for a combined 200-plus yards after averaging 148 yards the past four games. This will be the second game with Taylor back on the field, and coach Shane Steichen said he intends to give Taylor an increased role Sunday alongside veteran Zack Moss. The Colts are expected to lean heavily on their running game, with starting quarterback Anthony Richardson now on injured reserve and expected to miss four or more games because of a shoulder injury. — Stephen Holder
Stat to know: Lawrence has a 75 QBR (ranking fourth in the NFL) and a 7.7% off-target percentage (second lowest in the NFL) against zone coverage this season. That’s important because the Colts use zone coverage at the 10th-highest rate in the NFL.
Matchup X factor: Colts edge rusher Kwity Paye. He’s playing opposite Jaguars rookie tackle Anton Harrison (70.1%), who has the worst pass block win rate at tackle in the league. Paye has a chance to throw Lawrence off his game. — Walder
What to know for fantasy: The Colts’ defense has given up the ninth-most fantasy points per game to wide receivers. Calvin Ridley should be in fantasy lineups Sunday. He leads the Jaguars with 15.1 yards per reception. See Week 6 rankings. — Moody
Betting nugget: Minshew is 8-14 ATS in his past 22 starts. Read more.
Moody’s pick: Jaguars 28, Colts 23
Walder’s pick: Colts 23, Jaguars 21
FPI prediction: JAX, 65.5% (by an average of 5.5 points)
1 p.m. ET | FOX | Spread: NO -1.5 (42.5)
Storyline to watch: Two strengths will clash Sunday, as the Saints have allowed the sixth-lowest QBR (46.4), and their seven interceptions are tied for third most in the NFL. On the flip side, Texans rookie quarterback C.J. Stroud is third in passing yards (1,461) and hasn’t thrown an interception in an NFL-record 186 passes. — DJ Bien-Aime
Bold prediction: The Saints will end Stroud’s historic streak by giving him his first interception. They’ve already tied last season’s interception total, and they have an interception in four of five games (and a turnover in all of them). With the Saints’ knack for forcing turnovers this season, it seems like they could come out on top in that regard. — Katherine Terrell
Stat to know: New Orleans running back Alvin Kamara has 50 career rushing touchdowns, two shy of tying Mark Ingram for the most in Saints history. Kamara became the Saints all-time leader in total touchdowns (73) last week against the Patriots, passing Marques Colston.
Matchup X factor: Saints right tackle Ryan Ramczyk. He’s one of the best tackles in the league, but he has a key assignment against No. 3 overall pick Will Anderson Jr. this week. Anderson hasn’t had a sack in four games, but they’re coming, as he ranks fifth in pass rush win rate at edge. — Walder
What to know for fantasy: The Texans’ defense allows the seventh-most fantasy points per game to running backs, and Kamara has scored 19 or more fantasy points in two consecutive games. See Week 6 rankings. — Moody
Betting nugget: The Saints have gone under the total in 11 straight games, tied with the 2003 Bills for the longest such streak in the past 35 seasons. Read more.
Moody’s pick: Texans 20, Saints 17
Walder’s pick: Texans 27, Saints 17
FPI prediction: NO, 54.3% (by an average of 1.5 points)
Matchup must-reads: Could Saints’ stingy D be first to pick off Stroud? … Texans feel ‘very close’ to getting run game, Pierce on track … Moreau scores 1st TD since cancer diagnosis … Stroud sets record for passes without pick to start career
4:05 p.m. ET | CBS | Spread: LV -3 (41.5)
Storyline to watch: The Patriots have been outscored by a combined 72-3 in the past two games. The Raiders’ defense has given up just 13 points in the past six quarters while forcing four turnovers in that span. Yet the coaching staffs are so intimately familiar with each other, given so many New England ties on the Raiders’ staff, that recent history should be thrown to the wind. — Paul Gutierrez
Bold prediction: The Patriots, who have a league-low two takeaways, will match their season total against former Patriots QB Jimmy Garoppolo, who has thrown seven interceptions this season. Meanwhile, Raiders kicker Daniel Carlson, who set the NFL record for field goals of 50-plus yards last season (11) but is 0-for-2 on such attempts this year, will deliver his first from long range in 2023. — Mike Reiss
Stat to know: Raiders coach Josh McDaniels is 2-0 against Patriots coach Bill Belichick. He seeks to join Dave Wannstedt as the only coaches to defeat Belichick and the Patriots in each of their first three meetings.
Matchup X factor: Raiders edge rusher Maxx Crosby. We all saw what he can do Monday night against the Packers. Against a weak Patriots offensive line, the chance is ripe for a repeat performance. — Walder
What to know for fantasy: The Patriots wide receivers rank near the bottom of the league when it comes to creating separation, according to NFL Next Gen Stats. New England’s offensive line also ranks 30th in pass block win rate. It’s not a great combination for a struggling Patriots passing game. See Week 6 rankings. — Moody
Betting nugget: The Raiders are 0-3 ATS on short rest under McDaniels, with all three games going under the total. Read more.
Moody’s pick: Raiders 17, Patriots 14
Walder’s pick: Patriots 15, Raiders 12
FPI prediction: LV, 55.6% (by an average of 2 points)
Schefter joins McAfee to talk Belichick’s future with Patriots
Adam Schefter joins Pat McAfee to discuss Bill Belichick’s future with the Patriots. (edited)
4:25 p.m. ET | FOX | Spread: LAR -7 (48.5)
Storyline to watch: With running back James Conner on injured reserve because of a knee injury, the Cardinals don’t have another back with more than 48 rushing yards so far. But the Rams’ rush defense ranks 25th in DVOA and allowed 159 rushing yards to the Eagles in Week 5. — Sarah Barshop
Bold prediction: Cardinals quarterback Joshua Dobbs will make up for Conner’s absence and have the best game of his career. He’ll throw for more than 300 yards and rush for at least 100 against a Rams defense that ranks 16th in opponent scoring (21.6 points allowed per game) in the Cardinals’ second win of the season. — Josh Weinfuss
Stat to know: Dobbs has thrown six passing touchdowns through his first five games with the Cardinals. He needs four more to tie Gary Hogeboom for the most touchdown passes (10) through a player’s first six games with Arizona.
Matchup X factor: Cardinals running back Emari Demercado. With Conner injured, Demercado might be the one to carry the workload in his absence. We know the Cardinals will want to run the ball, so he should play a big role in this game. — Walder
What to know for fantasy: Rams QB Matthew Stafford has averaged 290.2 passing yards per game and has Cooper Kupp and Puka Nacua as his top two receivers. In terms of fantasy points allowed per game, Arizona’s defense has allowed the seventh-most points to wide receivers and the third most to quarterbacks. — Moody
Betting nugget: The Rams are 5-0-1 ATS in their past six games following a loss. Read more.
Moody’s pick: Rams 28, Cardinals 21
Walder’s pick: Rams 27, Cardinals 14
FPI prediction: LAR, 72.7% (by an average of 8.3 points)
Matchup must-reads: With Conner on IR, what’s next for Cardinals’ offense? … Nacua, Kupp tandem is a ‘champagne problem’ for Rams … First-quarter struggles keep putting Cardinals ‘behind the eight ball’ … McVay says Jefferson trade was best for both sides
4:25 p.m. ET | FOX | Spread: PHI -7 (41)
Storyline to watch: This game features two of the most productive running backs in the NFL — the Eagles’ D’Andre Swift (434 yards, fourth in rushing yards) and the Jets’ Breece Hall (387, sixth), who is coming off a 177-yard gem in a win over the Broncos. The Jets’ chances of pulling off the upset — and their first-ever win over the Eagles — hinge on a big game from Hall, who is fully recovered from last season’s ACL surgery. — Rich Cimini
Bold prediction: Eagles receiver DeVonta Smith will lead the way with 120-plus receiving yards. The Eagles’ skill players take turns dominating the stat sheet. A.J. Brown and Dallas Goedert have taken center stage in recent weeks. Coming off a one-catch outing against the Rams, Smith will emerge as the focal point to penetrate a Jets pass defense that has limited offenses to 206 passing yards per game and is tied for fourth in the NFL in interceptions (five). — Tim McManus
Stat to know: Eagles QB Jalen Hurts has 55 rushes (the most among QBs), 206 rushing yards (second most) and four touchdowns (tied for the most) this season. He’s facing the Jets who have allowed the second-most rushing yards to opposing QBs this season (163).
Matchup X factor: The Jets’ offensive line. Just as it was starting to figure things out, the line lost its best player in Alijah Vera-Tucker for the season. The group has its work cut out for it against the Eagles. It’s a big ask to protect Zach Wilson this week. — Walder
What to know for fantasy: The Jets are the only team in the league that averages more yards per rushing play (5.4) than passing play (5.0). The Jets’ offensive line ranks 13th in run block win rate, which bodes well for Hall. — Moody
Betting nugget: The Eagles are 12-0 outright and 11-1 ATS all-time against the Jets, with six straight covers. Read more.
Moody’s pick: Eagles 31, Jets 17
Walder’s pick: Eagles 28, Jets 16
FPI prediction: PHI, 65.3% (by an average of 5.4 points)
4:25 p.m. ET | FOX | Spread: DET -3 (43.5)
Storyline to watch: The leader of the NFC North faces the leader of the NFC South. The Lions’ offense is on fire, averaging 29.6 points per game — fourth best in the league — while the Bucs boast one of the league’s stingiest red zone defenses. The Bucs are holding opponents to a 27.3% efficiency rating in the red zone (second best), and opposing quarterbacks are completing just 33.3% of their passes in the red zone, the best mark in the NFL. — Jenna Laine
Bold prediction: Lions running back David Montgomery will rush for 100-plus yards for a third straight game. Tampa Bay’s rush defense is no slouch, allowing just 379 total rushing yards on the season, but Montgomery is in a groove, and the Lions continue to feed him. No Lions player has rushed for 100 or more yards in three consecutive games since Hall of Famer Barry Sanders (1998). — Eric Woodyard
Stat to know: The Buccaneers have allowed four sacks this season, which is the fewest allowed by the team through four games since 2008 (also four). The Lions have registered 14 sacks so far this season, tied for 14th-most in the NFL.
Matchup X factor: Lions wide receiver Jameson Williams. He had two receptions for 2 yards last week, but he played 47% of the snaps. I could see him making a big impact soon. — Walder
What to know for fantasy: The only teams with more rushing attempts than the Lions (165) are the Eagles (179) and 49ers (173). But the Buccaneers’ defense has held its opponents to fewer than 80 rushing yards in three of four games this season. See Week 6 rankings. — Moody
Betting nugget: The Lions are 27-12 ATS under coach Dan Campbell, the best record in the NFL in that span. They are 4-1 ATS this season with three straight covers. Read more.
Moody’s pick: Lions 31, Buccaneers 27
Walder’s pick: Lions 35, Buccaneers 13
FPI prediction: DET, 55% (by an average of 1.8 points)
Matchup must-reads: Mosely tears ACL for second year in a row … Mayfield’s Bucs renaissance, and what’s next … Goff: Lions becoming ‘more mature team’ … Confident Bucs embracing Bowles era on both sides of ball
The key to Baker Mayfield’s turnaround with the Bucs
Marcus Spears says Buccaneers QB Baker Mayfield is more comfortable and is playing free with fewer expectations this season.
8:20 p.m. ET | NBC | Spread: BUF -14 (45)
Storyline to watch: This game represents a big bounce-back opportunity for the Bills’ offense after a subpar performance against the Jaguars — especially for the ground game. The Giants have given up 5.3 yards per rush (29th) and 6.3 yards per play (31) this season. A Bills offense that scored 37-plus points in a three-game stretch before Week 5 will be a challenge for this Giants defense. — Alaina Getzenberg
Bold prediction: Giants RB Saquon Barkley will rush for 100-plus yards in his return from an ankle injury despite seeing fewer than 15 carries. This might seem improbable given the state of the Giants’ offensive line and Barkley’s track record after returning from ankle injuries. But the Giants’ line is better at run blocking than pass blocking (sure, it’s a low bar at this point), and Buffalo is beat up defensively. The Bills are allowing 134.0 rushing yards per game, 25th in the NFL. Welcome back, Saquon! — Jordan Raanan
Stat to know: The Bills have used nickel defense on 95.8% of their plays this season, the highest rate in the NFL. They have dominated opponents using five-plus defensive backs, ranking first in both touchdown-to-interception ratio and sack rate. The Giants, who struggle against defenses with five-plus defensive backs, rank last in those metrics.
Matchup X factor: Bills edge rusher Von Miller. He played just 23% of the snaps last week, but that presumably will be increasing against the Giants. And the Bills need the help, too, with DaQuan Jones now injured. — Walder
What to know for fantasy: New York’s defense has given up the fifth-most fantasy points to running backs so far this season. Don’t be afraid to start James Cook. See Week 6 rankings. — Moody
Betting nugget: The Giants are 0-5 ATS this season, the worst in the NFL. Last season, the Giants were 13-4 ATS, the best mark in the NFL. Read more.
Moody’s pick: Bills 38, Giants 17
Walder’s pick: Bills 30, Giants 17
FPI prediction: BUF, 89.3% (by an average of 17 points)
Storyline to watch: The Cowboys fired offensive coordinator Kellen Moore after last season’s divisional-round playoff loss, with coach Mike McCarthy taking over as the team’s offensive playcaller. The Chargers quickly scooped up Moore after firing their coordinator, Joe Lombardi, and Moore has the Chargers among the league’s best passing offenses. Now he will face his former team fresh off the Cowboys’ 32-point loss to the 49ers, in which the Cowboys scored just 10 points. — Kris Rhim
Bold prediction: Cowboys QB Dak Prescott will throw for 300 yards. That might be commonplace for many quarterbacks, but it hasn’t been common for Prescott. In his past 17 starts, he has one 300-yard game. The Chargers’ pass defense has had an every-other-game feel so far, allowing 466 and 367 yards in the first and third games. Maybe the bye will help Los Angeles, but Prescott could have a big night. — Todd Archer
Stat to know: Over the past three seasons, Herbert has been one of the league’s best QBs under pressure, ranking third in QBR (66.1), sixth in completion percentage (67.5%), second in passing yards (10,859), fifth in passing touchdowns (70) and third in sack rate when under pressure (15.5%). The Cowboys lead the NFL in pressure percentage over that same span.
Matchup X factor: McCarthy. He wanted offensive playcalling duties back, but so far the results haven’t been there. Dallas ranks just 15th in EPA per play on that side of the ball, with neither the passing game nor rushing game cracking the top 10. — Walder
What to know for fantasy: The Cowboys’ defense ranks 25th in run stop win rate (29.1%), while the Chargers’ offensive line ranks sixth in run block win rate (72.4%). For fantasy managers, L.A. running back Austin Ekeler‘s expected return comes at a great time. — Moody
Betting nugget: The Cowboys are 5-0 ATS after a loss in the past two seasons and 9-1 ATS in the past three seasons (seven straight covers). Read more.
Moody’s pick: Chargers 27, Cowboys 17
Walder’s pick: Chargers 30, Cowboys 23
FPI prediction: LAC, 55.4% (by an average of 1.9 points)