Patriots vs. Bills Prediction, Odds, Spread, Injuries, Trends for NFL Week 4

The New England Patriots and Buffalo Bills will begin their respective AFC East schedules in Week 4 of the NFL season when they face each other in an early-afternoon showdown.

The Patriots won the AFC East, and eventually the AFC, a year ago, but have stumbled out of the gate to begin the season, going 1-2 through the first three weeks. Meanwhile, the Buffalo Bills are off to a 3-0 start to the season, hoping to take the next step and make a deep run in the playoffs.

Let's dive into the odds and my best bet for this rivalry showdown.

Patriots vs. Bills Odds, Spread, and Total

Odds via BetMGM Sportsbook

Spread

Patriots +6.5 (-102)
Bills -6.5 (-118)

Moneyline

Patriots +270
Bills -325

Total

OVER 48.5 (-108)
UNDER 48.5 (-110)

Patriots vs. Bills How to Watch

Date: Sunday, October 4
Time: 1:00 pm ET
Venue: Highmark Stadium
How to Watch (TV): CBS
Patriots record: 1-2
Bills record: 3-0

Patriots vs. Bills Betting Trends

The OVER is 7-3 in the last 10 meetings between these two teams
Patriots are 7-3 against the spread in their last 10 games
The UNDER is 6-4 in the Patriots' last 10 games
Bills are 6-4 against the spread in its last 10 games
The OVER is 7-3 in the last 10 Bills' games

Patriots vs. Bills Key Player to Watch

Drake Maye, QB - New England Patriots

Drake Maye was the runner-up MVP a year ago, but things have not gone his way to begin the 2026 campaign. He has completed just 63.7% of passes for 585 yards, one touchdown, and six interceptions. Not only are his numbers worse than last year's, but they're far worse than his rookie numbers in 2024. He has to turn things around in a hurry.

Patriots vs. Bills Prediction and Best Bet

In the Week 4 edition of the Road to 272 Bets, I broke down why I'm taking the points with the Patriots:

It's time to buy low on the New England Patriots. I wasn't high on them coming into this season, but they're not as bad as they've shown so far this season. RBSDM.com has the Patriots ranking last in their offensive luck index. Things have not bounced their way, but I expect them to show some level of life in the coming weeks. They rank ninth in the NFL in Net Yards per Play (+0.3), and their defense ranks in the top half of the NFL in both opponent EPA per play and opponent success rate.

The Bills' defense is going to come back to haunt them at some point. They're 25th in opponent EPA per play, 27th in opponent success rate, and 19th in opponent yards per play (5.4). Even with your offense being elite, it's going to be hard to win by margin with that defense.

I'll take the points with New England.

Pick: Patriots +6.5 (-102) via BetMGM

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