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Patriots vs Bills Predictions, Picks & Sunday Night Football Odds

Brady Trettenero

By Brady Trettenero in NFL News

Published:


Sep 28, 2025; Foxborough, Massachusetts, USA; New England Patriots quarterback Drake Maye (10) looks to throw against the Carolina Panthers during the first half at Gillette Stadium. Mandatory Credit: Brian Fluharty-Imagn Images
  • The Bills are 8-point home favorites over the Patriots in Week 5 Sunday Night Football odds
  • Buffalo’s defense is decimated with both Dorians out, Matt Milano and Ed Oliver questionable
  • See my Patriots vs Bills predictions and Sunday Night Football picks below, plus the latest betting odds

The Bills enter Sunday Night Football undefeated at 4-0, but their defense is falling apart. Matt Milano and Ed Oliver are both questionable after limited practice all week. Dorian Williams and Dorian Strong are both out. That’s four defensive starters either sidelined or compromised for a primetime divisional matchup.

The Patriots (2-2, 1-1 away) have covered four straight against Buffalo despite being underdogs every time. Drake Maye gets his best matchup yet against this banged-up defense. Meanwhile, the Bills have struggled to contain the run despite their 4-0 record.

Kickoff is scheduled for 8:20pm ET from Highmark Stadium in Orchard Park, NY, with NBC providing the broadcast coverage.

Patriots vs Bills Prediction and Pick

Sports Betting Dime •

Pick
Odds
Over +48.5
Over/Under
NFL • New England Patriots @ Buffalo Bills
-110 on Caesars
SCHEDULED • 10/06/2025
Tally (Win %)
0-0-0 (0%)
Money Meter
$0.00
ROI
0.0%
Betslip #1759638468717-481c-494

The sharp money has this one figured out. The total has steadily climbed from 46.5 to 49.5, with 70.7% of the money on the Over. However, there are only 41% of bets, meaning the wagers are substantial. The sharps are seeing what we can all see: the Bills’ defense has major holes.

Without Milano, the Bills lose their best coverage linebacker. Hunter Henry should feast over the middle. His 41.5 receiving yards line looks too low. Ed Oliver hasn’t played since Week 1 after getting stepped on in practice. If he can’t go, that removes their interior pass rush and gives Maye time to find his receivers.

The spread gets interesting. The Patriots are 4-0 ATS in their last four meetings with Buffalo. They’ve kept every game close despite being outgunned on paper. Now they catch the Bills at their most vulnerable defensively. While I’m not officially playing the spread, the Patriots +8 has some value.

My favorite player prop is Allen’s interception at +125. The Patriots are a feisty defensive team with three interceptions forced this season. New England’s defense thrives on creating mistakes, having picked off Geno Smith, Tua Tagovailoa, and Aaron Rodgers already this season.

The high-scoring total suggests we will see plenty of points and a potential shootout. Allen has done an excellent job taking care of the football since the early days of his career, but he did throw his first pick of the season last week vs New Orleans.

I think Allen will be asked to pass more on Sunday with the holes in the Bills’ defense. The Patriots have a talented corner group, including a healthy Christian Gonzalez, to capitalize on this aggressive approach. I’m taking the plus money on back-to-back interception weeks for Allen, considering the high over/under in this game.

The score projection aligns with historical trends. The Over has hit in four of the last five meetings between these teams. Meanwhile, Buffalo has gone Over in all three home games this season. With perfect weather conditions and both teams facing defensive limitations, expect fireworks.

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NE vs BUF Player Props to Target

Hunter Henry over 41.5 receiving yards is the best New England player prop on the board. Milano’s absence creates a massive hole in coverage. Henry needs just approximately four catches to clear this number against backup linebackers.

Rhamondre Stevenson’s rushing line sits at just 30.5 yards. That’s disrespectful against a Bills defense missing multiple starters. The Patriots will lean on their ground game to control the clock and keep Allen on the sideline. With Jahlani Tavai back from injured reserve, New England’s run blocking should improve.

NE Patriots vs BUF Bills Betting Odds

Bet TypePatriotsBills
Spread+8 (-110)-8 (-110)
Moneyline+335-431
TotalO 49.5 (-110)U 49.5 (-110)

The line opened at Bills -9.5, but buyback brought it to -8 in the Sunday night football odds. The moneyline moved from -385 to -431 as money poured in on Buffalo to win outright.

But the real story is the total. Sharp bettors hammered the Over, driving it from 46.5 to 49.5. That three-point jump signals overwhelming professional action.

According to the NFL public betting percentages, 59.9% of bets are on the Under, but 70.7% of money backs the Over. Classic sharp versus square disagreement.

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Odds as of Oct. 5 at NFL betting apps. Shop multiple books for the best Patriots vs Bills betting lines.

New England vs Buffalo Matchup Analysis

The Bills have won 14 straight home regular-season games. They’re 15-4 in primetime since 2022. But they’ve never faced this Patriots team with their defense this compromised.

Buffalo allows just 77.5 rushing yards per game when healthy. Without Oliver clogging the middle and Milano filling gaps, those numbers become irrelevant. Stevenson and Antonio Gibson should find running lanes all night.

Josh Allen needs one win to become the first reigning MVP to start 5-0 since Aaron Rodgers in 2015. He has 45 career games with both a passing and rushing touchdown, tied with Cam Newton for the most by any player in NFL history. But the Patriots’ defense creates turnovers at a high rate.

TrendRecord
Patriots ATS vs Bills4-0 (Last 4)
Over in Series4-1 (Last 5)
Bills Home vs NE3-0 SU (Last 3)
Bills Primetime15-4 (Since ’22)

Patriots vs Bills Injury Report

Buffalo’s injury list reads like a casualty report. Dorian Williams (knee) and Dorian Strong (neck) are both out. That’s two defensive starters who won’t play. Strong was placed on injured reserve Saturday, leaving the Bills thin at cornerback.

The bigger concerns are Matt Milano (pectoral) and Ed Oliver (ankle). Both were limited all week and are questionable. Milano is their defensive quarterback who makes all the coverage calls. Oliver hasn’t played since Week 1 after getting stepped on in practice and just returned to limited work this week for the first time in 20 days.

New England’s injury report has its own issues. K’Lavon Chaisson (knee) was ruled out Saturday after missing Friday’s practice. The linebacker has 2.5 sacks this season, second on the team, and plays 68.3% of defensive snaps. Without him, Keion White steps into a larger role.

The good news? Jahlani Tavai was activated from injured reserve. The veteran linebacker led New England with 115 tackles last season and provides veteran leadership alongside Robert Spillane. Milton Williams (ankle) is questionable but traveled with the team.

The market movement tells you everything. Sharp money drove the total up three full points. With Buffalo’s defense this depleted, both offenses should put up numbers. Even the Bills’ punter situation is a mess – they’re on their third punter in five weeks after Cameron Johnston went to IR.

I’m taking the Over 49.5 and Allen to throw a pick as my Patriots vs Bills predictions for Sunday Night Football. The injuries are too significant to ignore.

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Brady Trettenero
Brady Trettenero

Lead NHL & NCAAF Editor

Brady is the lead NHL and College Football editor at Sports Betting Dime, where he specializes in betting odds and data-driven analysis. Brady has over 10 years experience working in sports media, with work published by outlets such as ESPN, CBS Sports, Yahoo! Sports and Fox Sports.

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