New England Patriots vs. Buffalo Bills Picks and Prediction, Sunday, October 5th, 2025

In this Patriots at Bills prediction, the Patriots travel to Buffalo to take on the Bills in an AFC East clash on Sunday night. The Patriots come into this game with a record of 2-2 after blasting the Panthers in New England in week four. The Bills remained perfect at 4-0 after taking down a feisty New Orleans Saints team in Buffalo last week. The opening kick is scheduled for 8:15 pm EST. If you need quality winners, this is the ultimate site for NFL Picks.

New England on the road again

The New England Patriots come into Buffalo looking for their second straight win after dismantling the Carolina Panthers in Foxboro last week, 42-13. Leading the Panthers 7-6 after one quarter, the Patriots outscored the Panthers 21-0 in the second quarter and rolled to their second win of the season. One week after turning the ball over five times in a loss to the Steelers, New England protected the football and dominated the Panthers.

"When we don’t beat ourselves and we take care of the football and we play complementary football ... it can look like something," Head coach Mike Vrabel said.

The Patriots were led by quarterback Drake Maye on Sunday. Maye was an efficient 14-of-17 for 203 yards. He ran for a touchdown and threw for two touchdowns, one to Mack Hollins and the other to Hunter Henry. Wide receiver Steffon Diggs had his best game as a Patriot with six catches for over 100 yards. The Patriots also got a dynamic 87-yard punt return for a touchdown from cornerback Marcus Jones. The Pats finished with 307 yards of total offense and had three rushing touchdowns in total.

Defensively, the Patriots held the Panthers to 326 yards of total offense. Linebackers Jack Gibbens and Robert Spillane combined for 25 tackles, and Gibbens recovered a fumble. The Patriots had two sacks in the game and five tackles for loss. After allowing a touchdown on the Panthers’ opening drive, the Patriots shut out the Panthers until midway through the fourth quarter.

The Patriots come into this game ranked 10th in the NFL in points per game. They are 24th in rushing and seventh in passing. The Pats are fifth in the NFL in the red zone. They are 26th in sacks allowed. The Patriots are just 31st in the league in red zone defense. They are 12th in sacks per game. They are 25th in penalties per game and 26th in turnover margin.

Key Injuries: LB Marte Mapu, CB Carlton Davis III, LB K’Lavon Chaisson, S Jaylinn Hawkins, and DE Milton Williams are out.

Bills still perfect

The Buffalo Bills got a scare from the visiting New Orleans Saints on Sunday, but in the end, they remained perfect with a 31-19 win. The Bills led 14-10 at the half and led by just two in the fourth quarter before scoring the game’s final ten points to pull away. As usual, MVP quarterback Josh Allen was in the thick of it all, leading the Bills to the win.

“We weren’t doing ourselves many favors. A couple of boneheaded penalties, boneheaded mistakes,” said Allen, who went 16 of 22 for 209 yards and threw his first interception of the season. “Throwing a pick doesn’t help.”

Allen put on his Superman cape in the fourth quarter, up by just two. Allen ran for 27 yards and followed that up with a 29-yard touchdown pass to tight end Dalton Kincaid to put the Bills comfortably in the lead. Running back James Cook kept his hot play going with 117 yards rushing and a touchdown. Wide receiver Khalil Shakir added a 43-yard touchdown as well. In all, the Bills had 356 yards of total offense, including 165 on the ground.

The Bills’ defense allowed 298 yards of total offense, including just 108 yards through the air. The Bills forced one turnover in the game, an interception from Cole Bishop. Cornerback Tre’Davious led the Bills with seven tackles, including one tackle for loss. The Bills held the Saints to 5-for-15 on conversions.

The Bills are second in the NFL in points per game. They are seventh in the league in rushing and sixth in passing. The Bills are second in the NFL in red zone offense, and they are 10th in sacks allowed. On the defensive end, the Bills are 17th in scoring defense. They are 30th in the league against the run and first in the league against the pass. The Bills are 21st in red zone defense. They are 19th in sacks per game. The Bills are ninth in penalties per game and sixth in turnover margin.

Key Injuries: CB Dorian Strong, DT TJ Sanders, LB Matt Milano, DT Ed Oliver, and LB Dorian Williams are questionable.

Patriots vs. Bills Pick

Point Spread Pick for Patriots vs. Bills 

• Patriots +7.5 (4 units)

The Patriots have won each of their four games this season, with the win over the Panthers the only blowout. The Patriots will test the Bills' defense, which is ranked #1 against the pass. Digging a little deeper, however, and, thus far, the Ravens’ Lamar Jackson represents the only upper-level quarterback the Bills have played. On Sunday night, they’ll have to contend with Patriots quarterback Maye, who leads the NFL in completion percentage. Maye’s biggest avenue of success might be throwing to his running back out of the backfield. Buffalo has had issues with running backs this season, and New England will surely utilize their three backs both on the ground and in short passing plays. The Patriots also have Gonzalez back at QB, which gives them a cornerback who can be left alone in coverage. That will give the Pats’ defense added support on the other wideouts. This one should be tight. I’m taking the points.

Take the Patriots +7.5

Over/Under Pick for Patriots vs. Bills 

• Over 49.5 

The Bills have gone over the total in three of their first four games this season. They are ranked second in the league in scoring. Quietly, the Patriots are ranked 10th in the NFL in scoring. The Patriots have also scored over 30 points in each of their two wins this season. These two teams are each in the top five in converting red zone opportunities into touchdowns. Expect a back-and-forth contest that goes over the number.

Take the over 49.5