NFL Prediction Panel Likes Bills' Chances to Deliver Crushing Blow vs. Patriots

The Buffalo Bills lost an early game last season to the New England Patriots, and it essentially opened the door for their rivals to reclaim the division crown.

This year, however, the Bills have a prime opportunity to put the Patriots in a deep hole through the first one quarter of the regular season schedule. The 3-0 Bills can move 3.0 full games ahead of New England (1-2) in the AFC East race by winning at home on October 4.

“We're not the same as we were last year. They're not the same as they were last year. It's two teams that are just still trying to figure out who they are at this point in the season. It's going to be great football," said Bills' rookie head coach Joe Brady, who was promoted from offensive coordinator this past offseason.

Sep 27, 2026; Orchard Park, New York, USA; Buffalo Bills head coach Joe Brady speaks with the referee during the second half against the Los Angeles Chargers | IMAGN IMAGES via Reuters Connect

While the Bills are off to a roaring start, the Patriots have totaled only 36 points over their first three games. When it comes to New England's struggles, Sports Illustrated's experts predict them to continue this week in Orchard Park.

The eight-member panel of prognosticators unanimously picked Buffalo to defeat the Patriots in Week 4. Of the 16 games on the slate, the panelists completely agreed on five of them. As always, the SI picks are straight up.

As for the betting line for Sunday, the Bills are a 7.0-point home favorite (per DraftKings). In addition to winning all three games outright to start the season, Buffalo is 3-0 against the spread.

With Patriots' quarterback Drake Maye mired in a slump, having connected on only one touchdown pass compared to being intercepted six times, the Bills will look to keep the heat on through their surprisingly potent pass rush, especially considering the state of New England's banged-up offensive line. SI identified the Patriots' ability, or inability, to run the ball effectively as the biggest variable heading into Sunday.

Sep 13, 2026; Houston, Texas, USA; Buffalo Bills defensive tackle Deone Walker (96) tackles Houston Texans running back Woody Marks (4) | IMAGN IMAGES via Reuters Connect

Although Buffalo will likely be without top cornerback Christian Benford, Patriots' WR1 AJ Brown remains on Injured Reserve.

On the other side, Josh Allen and the Bills' offense have to face a Patriots' defense that can cause problems in a hurry. On the plus side for Buffalo, cornerback Christian Gonzalez has been ruled out, which could mean a big day ahead for Bills' wide receiver DJ Moore.

"They were an outstanding defense last season. Through three games, they haven't taken any drop-offs. And it's a hard game plan. It's a hard team to game plan for," said Brady.

The 1 p.m. ET kickoff will air live via CBS. It will be the final leg of the Bills' three-game home stand that began with a September 17 primetime win over the Detroit Lions.

Bills running back James Cook III celebrates his fourth quarter touchdown against the Chargers with teammates Connor McGovern and Spencer Brown during their game Sunday, September 27, 2026 at Highmark Stadium in Orchard Park, NY. | USA TODAY Network via Reuters Connect

MMQB Game Picks (Week 4)
Bills vs. Patriots

Albert Breer, senior reporter
Pick: Bills

Eva Geitheim, staff writer
Pick: Bills

Mitch Goldich, senior editor
Pick: Bills

Mike Kadlick, senior news writer
Pick: Bills

Gilberto Manzano, staff writer
Pick: Bills

Conor Orr, senior writer
Pick: Bills

John Pluym, managing editor
Pick: Bills

Matt Verderame, staff writer
Pick: Bills

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MMQB Game Picks (Week 4)Bills vs. Patriots

MMQB Game Picks (Week 4)
Bills vs. Patriots