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Patriots vs. Bills Prediction: Week 4 Odds, Picks & Best Bet

Our Patriots vs. Bills prediction for Week 4 includes our best bet, projected score, and the latest odds for Sunday's matchup.

Matt MacKay

Last Updated: October 4, 2026 9:47 AM EDT • 3 minute read

Pictured: Patriots quarterback Drake Maye (10) looks to pass as we break down our Patriots vs. Bills prediction. Photo by Corey Perrine / Florida Times-Union.

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An AFC East rivalry between former and current NFL MVP betting favorites is the biggest narrative in my latest Patriots vs. Bills prediction. Drake Maye will attempt to resolve his turnover woes today, while Josh Allen looks to keep the Bills undefeated in 2026.

The Bills are a 7-point betting favorite in their new confines at Highmark Stadium in Orchard Park, N.Y., with kickoff set for 1 p.m. ET (CBS).

🏈 Patriots vs. Bills picks & predictions

See all of our experts' NFL picks for Week 4 based on the latest NFL odds.

Pick	Bet size
Patriots +7 (-115 via bet365)	2.3 units
Under 50.5 (-115 via bet365)	1.15 units

Total wagered: 3.45 units | Max profit: +3 units

💰 Patriots vs. Bills prediction & best bet

Patriots +7 (-115 via bet365)

The Patriots are coming off a dispirited performance in Jacksonville, losing 35-6 to the Jaguars in Week 3. Maye's thrown 1 touchdown and 6 interceptions, while getting sacked 3 times in every start this season.

Buffalo has a big vulnerability that New England can exploit. The Bills' run defense has surrendered 124+ rushing yards to the Texans and Chargers. Patriots running backs TreVeyon Henderson and Rhamondre Stevenson should take on an increased role early in this game to stay ahead of schedule and keep Allen off the field.

It gets even better knowing that 68 percent of public money is laying Buffalo -7.0 in this game. Maye's in a favorable matchup to cure his bad play, since he can lean on the run game. Bills edge rusher T.J. Sanders is also doubtful, which gives the Patriots' offense a boost.

Allen threw 2 interceptions and failed to log a passing touchdown against the Chargers at Highmark Stadium in his last start. While New England's playing without star CB Christian Gonzalez and DE Christian Barmore, the Patriots have still held opponents under 200 passing yards in every matchup.

Go to bet365 and bet on the Patriots +7.0 at -115 odds.

📡 SBR Edge: Patriot Pride

The Patriots have covered the spread in 5 of their last 6 games against the Bills.

Patriots' rushing attack gives Bills a scare

The Bills' porous run defense is the antidote that Maye needs to overcome his bad play under center. Patriots head coach Mike Vrabel knows he needs Henderson and Stevenson to have a big game, so expect 30+ carries between both running backs, which will also set up explosive play-action pass attempts for Maye.

Allen and the rest of Buffalo's offense are going to find a way to win this game to improve to 4-0. However, divisional matchups are tough due to familiarity. The Patriots are a desperate team that can exploit the Bills' weakness to grind clock and move into scoring position, giving the Bills a scare at Highmark Stadium.

Score prediction: Bills 24, Patriots 20

📊 Patriots vs. Bills odds

See the latest NFL odds for every Week 4 matchup.

Patriots vs. Bills opening odds

Moneyline: Patriots +150 | Bills -185
Spread: Patriots +3.5 (-110) | Bills -3.5 (-110)
Over/Under: Over 49.5 (-112) | Under 49.5 (-108)

📺 How to watch Patriots vs. Bills: Week 4

Date: Sunday, Oct. 4
Kickoff: 1 p.m. ET
Location: Highmark Stadium (Orchard Park, N.Y.)
TV: CBS

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Written by:
Matt MacKay

Matt MacKay has handicapped golf, the NFL, NCAAF, and NHL since joining the sports betting industry as a writer in 2020. He’s worked for several prominent sites, recently expanding his coverage to include sports betting news and the regulatory industry. Bringing a background in communications and writing, earning a Masters Degree in Organizational Communication from Ohio University, Matt has co-hosted a fantasy football and sports betting podcast, while continuously refining his handicapping methods. This includes identifying recent trends, head-to-head statistics, and comparing individual and team strengths and weaknesses to accurately predict the outcome in certain betting markets before a game or event. He’s a daily bettor and tends to wager on FanDuel, with DraftKings and Hard Rock Bet as preferred sports betting app alternatives. An avid researcher, writer, editor, and podcaster, Matt is eager to dig into matchups to offer readers and subscribers value on his picks. He’s a big proponent of building bankroll by avoiding poor betting habits and tendencies, like chasing losses, placing too many wagers, and managing bankroll. His worst beats to date both came on two separate NFL parlays, losing due to Tyreek Hill and A.J. Brown dropping passes. NRFIs have quickly become one of Matt’s favorite betting markets, recently diving into MLB game props.