Patriots at Bills Predictions, Odds and Betting Picks
The Buffalo Bills are the clear moneyline favorite against the New England Patriots, with BetMGM listing Buffalo at -325 and the Patriots at +270. Josh Allen has thrown for 786 yards and five touchdowns through three games, while Drake Maye has six interceptions against one touchdown. Those numbers make the quarterback matchup the central angle for these NFL Picks.
Buffalo also brings the league's No. 1 scoring offense at 33.7 points per game, while New England ranks 31st at 12 points per game. The Patriots have struggled to protect Maye, who has already taken 9 sacks, and the Bills have recorded 9 sacks through three games. This Statistical analysis of NFL teams points toward a clear advantage for Buffalo.
Patriots vs Bills Game Preview
The Bills are 3-0 and have covered all three games against the spread, while the Patriots are 1-2 with a 2-1 ATS record. Buffalo averages 401.7 total yards and 33.7 points per game, compared with 307 yards and 12 points for New England. Allen has a 104.12 passer rating, while Maye has a 58.59 rating through three starts.
New England has several offensive line concerns, with Michael Onwenu on IR, Greg Van Roten injured and Morgan Moses questionable. Buffalo has T.J. Sanders ruled out, while Ed Oliver and Keon Coleman are questionable. The Patriots are also playing their second straight road game and making their first regular-season visit to the new Highmark Stadium, adding another factor to the Trends in NFL team performance entering this matchup.
Patriots vs Bills Moneyline Pick
Take the Buffalo Bills moneyline at -325 at BetMGM. Allen's 104.12 passer rating and 786 passing yards give Buffalo a major advantage over a Patriots offense led by Maye, who has six interceptions against one touchdown. The Bills are also averaging 401.7 total yards per game, compared with 307 for New England.
Buffalo's rushing attack adds another advantage. James Cook has 346 rushing yards on 58 carries, averaging 5.97 yards per carry, and the Bills average 155 rushing yards per game. The -325 price is steep, but the Statistical analysis of NFL teams supports Buffalo based on quarterback efficiency, rushing production and scoring output.
Pick: Bills ML (-325 at BetMGM).
Against the Spread Pick
Take Patriots +6.5 at -102 at BetMGM. The 6.5-point spread is close to the key number of 7, giving New England room to cover in a one-score Buffalo win. The Patriots have also covered two of their first three games despite averaging only 12 points per game.
The ATS case differs from the moneyline because it focuses on the margin. Buffalo has scored 101 points in three games, while New England has 7 sacks and 2 interceptions. A 27-21 result would give Buffalo the win while letting the Patriots cover, shaping these NFL predictions.
Pick: Patriots +6.5 (-102 at BetMGM).
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Patriots vs Bills Game Total Pick
Take the Under 48.5 at -110 at BetMGM. New England has not had a game finish over its total this season and is averaging only 12 points per game. Maye's six interceptions and 9 sacks create additional turnover and stalled-drive risks against a Buffalo defense that has recorded 9 sacks through three games.
The weather forecast calls for 66°F, partly cloudy skies and 11-12 mph south winds. New England's offense is the bigger concern, while Buffalo can lean on Cook's 5.97 yards per carry. These Trends in NFL team performance support a game staying below 49 points.
Pick: Under 48.5 (-110 at BetMGM).
How to Watch Patriots vs Bills and Game Info
- Location: Highmark Stadium, Orchard Park, New York.
- Date: Sunday, October 4, 2026
- Kickoff: 1:00 p.m. ET
- TV: CBS
- New England Patriots starting quarterback: Drake Maye (1-2, 585 yards, 1-6).
- Buffalo Bills starting quarterback: Josh Allen (3-0, 786 yards, 5-2).
- Weather forecast: 66°F, partly cloudy, wind out of the south at 11-12 mph.
Final Takeaways
Buffalo has the stronger offense, led by Allen's 104.12 passer rating and 33.7 points per game. The Bills are the moneyline pick at -325, while the Patriots are the spread pick at +6.5 after covering twice in three games. The total pick is Under 48.5 at -110, backed by New England's 12-point scoring average. These NFL Picks use the quarterback gap, Buffalo's rushing production and Statistical analysis of NFL teams.
Check the latest odds and line movement for Patriots vs Bills at betting.net before placing your bets. All odds as of 3:19 a.m. ET on September 30, 2026. Odds sourced from BetMGM.