Game Odds and Pick: New England Patriots at Buffalo Bills

Game Info:

Matchup: New England Patriots at Buffalo Bills
Date: Sunday, October 5, 2025
Time: 8:21 PM EST
Spread: Bills -8.5
Total (Over/Under): 49.5

AFC East Rivals Clash Under Sunday Night Lights

A classic AFC East rivalry gets the primetime treatment as the New England Patriots travel to Highmark Stadium to take on the Buffalo Bills. The Bills enter as heavy 8.5-point favorites, a reflection of their recent dominance in the division and the ongoing rebuild in New England. With a high total of 49.5 points, oddsmakers are expecting offensive fireworks, and the key to this game may lie in which team’s defense can get a critical stop.

The Case for the Buffalo Bills

The Bills are once again leaning on their high-powered offense to set the tone. At home and under the lights, expect Buffalo to be aggressive from the start, looking to test a Patriots secondary that has been dealing with significant injuries. While the Patriots once enjoyed an eight-game winning streak in Buffalo (2012-2019), the tables have turned, and this is now Buffalo’s rivalry to lose.

However, the Bills are not without their own health concerns. The team will be without defensive tackle T.J. Sanders, who was ruled out for the game with a knee injury. Throughout the early part of the 2025 season, key offensive players like running back James Cook (hamstring/toe) and wide receiver Khalil Shakir (ankle) have also appeared on injury reports, highlighting that Buffalo’s depth may be tested as the season progresses.

The Case for the New England Patriots

Coming in as significant underdogs, the Patriots face an uphill battle. For New England to keep this game close, they will need to control the clock with their running game and avoid a shootout. The challenge, however, lies on the defensive side of the ball.

The Patriots’ secondary has been hit hard by injuries. Star cornerback Christian Gonzalez was ruled out of a Week 2 matchup against the Dolphins with a hamstring issue that has reportedly lingered since late July. His status against Buffalo’s elite passing attack is the single biggest concern for New England. With defensive end Keion White also missing time earlier in the season, the Patriots’ defense will need a “next man up” mentality to have any hope of containing the Bills.

Key Matchup

Buffalo’s Passing Attack vs. New England’s Secondary

This is the matchup that will likely decide the game. If Christian Gonzalez is out or limited, the Patriots’ defensive backfield will be severely shorthanded against one of the league’s most dynamic offenses. The Bills will almost certainly look to exploit this potential weakness early and often. How New England’s defensive scheme holds up against Buffalo’s receivers will determine if this game stays within the 8.5-point spread or turns into a blowout.

Prediction

The Bills are at home, in primetime, and field the more talented and complete roster. While the Patriots will fight hard in this divisional slugfest, their injuries in the secondary are a critical liability against this particular opponent. Buffalo has too much offensive firepower, and it’s difficult to see a path for the Patriots’ offense to keep pace on the scoreboard.

Buffalo should be able to dictate the tempo of this game from the start. Look for them to win comfortably and put up enough points to push the total over the mark.

Final Score Prediction: Bills 31, Patriots 20