Buffalo Bills vs. New England Patriots Picks, Odds, Player Props and Predictions for Week 4

After nearly winning the MVP award last year, Drake Maye’s production has fallen off a cliff, throwing just one touchdown and six interceptions in three games. Heading into a divisional matchup against the Buffalo Bills, Maye will have a great opportunity to round back into form by picking apart a secondary that struggles in coverage.

New England Patriots vs. Buffalo Bills Betting Odds For Week 4

• Spread: Bills -7 (-105, DraftKings)
• Moneyline: Bills (-290, DraftKings)
• Game Total: 48.5 (Over -115/Under -105, theScore Bet)

Last year’s favorable schedule aside, Maye was still as efficient as it gets during his 2025 campaign, leading the league in QB EPA per play and CPOE. Even when surrounded by a weak group of skill players, Maye was still able to move the ball down the field with ease.

With Maye struggling to recapture the same success he had last year, his lack of production has been a thorn in the New England Patriots' side, making it difficult to compete. Oddsmakers are in agreement with that sentiment, listing the Patriots at +7 against the Buffalo Bills in most sportsbooks.

Fortunately for the Patriots QB, Maye will be able to break out of his slump by attacking a Bills defense that ranks 24th overall in dropback EPA allowed per play. With positive regression looming large over Maye, the Patriots will be able to match the Bills' output and keep it close enough to cover the spread.

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Prediction & Pick For New England Patriots vs. Buffalo Bills Week 4 Matchup

• The Pick: Patriots +7 (-115, DraftKings)

Buy low and sell high, a key phrase every sports bettor should have burned into their brain when navigating an odds board. The Patriots are a prime example for this weekend's slate with the spread dipping down to +7, making them worth a wager at a key number.

Even though the Bills have looked like a juggernaut three games into the season, they are far from perfect, fielding a defense that struggles to hold opponents in front of the sticks, per bottom-15 marks in defensive DVOA and EPA. With the secondary giving up ground to opposing pass catchers, Maye will be able to keep the Patriots close enough to the line to gain to help convert on later downs, making it easier to march down the field.

On the other side of the ball, Josh Allen faces his toughest test to date with the Patriots secondary residing near the top of the board in defensive pass DVOA. With New England’s corners capable of holding their own in coverage, the Patriots can spy linebackers on the edges and neutralize Allen’s legs when he tries to scramble out of the pocket.

With the Bills being held into early outs at a higher rate, the Patriots' total number of possessions on offense will increase, leading to an uptick in scoring opportunities. Getting the ball out of Allen’s hands will also help New England avoid playing in a highly volatile track meet, swinging variance towards the Patriots' way as a sizable underdog. Back the Patriots to cover the spread at no lower than the key number of +7.

Best Player Prop Bet For New England Patriots vs. Buffalo Bills

TreVeyon Henderson - o40.5 Rushing Yards (-108, FanDuel)

When healthy and out of Mike Vrabel’s doghouse, TreVeyon Henderson has been efficient with his opportunities, ranking in the top half of the position in yards over expected per attempt while averaging 4.1 yards per carry. Even when outperforming Rhamondre Stevenson, Henderson is still locked into a committee, lowering his ceiling as a rusher.

Against the Bills, Henderson will be able to strengthen his claim as the Patriots' RB1 by consistently gashing a front seven that ranks 27th in defensive rush success rate. Even with the Bills' defensive line generating pressure at a high rate, the second level has struggled to plug the gaps in the trenches. This will allow Henderson to generate more yards after contact, increasing his chances of clearing the over of 40.5 on his rushing yardage prop.