NE vs BUF Prediction, Odds and NFL Picks for Sunday, 10/04/26

The Bills captured the AFC East title five consecutive times prior to the Patriots snapping that streak in 2025. However, the defending AFC champions have stumbled to a 1-2 start this season, capped off by a 35-6 setback at Jacksonville. The Patriots have been held to 36 total points in the first three games, while scoring only two offensive touchdowns.

Buffalo plays for the third consecutive week at the brand-new Highmark Stadium, beating the Lions and Chargers to improve to 3-0. The Bills overcame five turnovers, including three from QB Josh Allen, in last Sunday’s 24-16 victory over the winless Chargers.

Buffalo has dealt with several issues defensively, including ranking 24th in EPA/Pass and 23rd in EPA/Rush. New England will try to take advantage, although the Pats sit 26th in EPA/Pass and 24th in EPA/Rush offensively. Last season, the road team captured each matchup with both games decided by a total of seven points. The Patriots held off the Bills 23-20 as 7.5-point road underdogs, but blew a 21-0 lead in a 35-31 home defeat last December.

The key to New England slowing down this Buffalo offense is controlling James Cook and the running game. Buffalo is first in EPA/Rush, facing a New England defense that ranks 28th in EPA/Rush, despite the Pats holding two opponents to fewer than 100 rushing yards. This is a good buy-low spot on the Patriots to cover against a Bills’ team they played tough in both matchups in 2025.

Patriots vs Bills prediction: Patriots +6.5 (+100) available at time of publishing. Playable to 6 (-110).

The Patriots are one of two teams in the NFL that have yet to register an over, along with the Chargers. New England and its opponents have combined to score 23, 23, and 41 points, while Buffalo combined for less than 50 points for the first time last week in its comeback win over Los Angeles.

The Pats have scored 13 or fewer points in four of the past five games since last season’s playoffs, with their highest output coming in the Week 2 win over Pittsburgh (20 points). Both matchups last season saw contrasting scoring outputs, with 43 points put up in Buffalo and 66 points in Foxborough.

Buffalo’s defense yielded 31 points in each of the first two wins over Houston and Detroit, but the Chargers couldn’t take advantage of five Bills turnovers, scoring only one touchdown. New England ranks 27th in offensive success rate at 40.1%, but is tied for 12th in defensive success rate at 42.2%.

Stopping Buffalo’s explosive plays will be a key to keep this a lower-scoring game. The Bills have compiled 37 explosive plays, compared to New England holding opponents to 17 such plays. New England still has to prove it can score, but the Pats can slow down the Bills’ offensive attack and have held Josh Allen to less than 253 passing yards in each of the two matchups last season.

Patriots vs Bills prediction: Under 48.5 (-105) available at time of publishing. Playable to 47.5 (-110).