Patriots linebacker Jamie Collins forced Buffalo's fourth turnover by intercepting backup Matt Barkley's pass with 1:27 remaining to seal New England's 16-10 win over the Bills on Sunday.
J.C. Jackson had two interceptions and blocked a punt, which was returned 11 yards by Matthew Slater for a touchdown. Brandon Bolden scored on a 4-yard run in a defensive slugfest between previously unbeaten AFC East rivals.
New England is off to its first 4-0 start since 2015, and fifth time during Bill Belichick's 20 seasons as coach.
The Bills (3-1) not only blew an opportunity to open a season with four straight wins for the first time since 2008, but now face questions at quarterback.
Barkley took over after starter Josh Allen sustained a head injury after being brought down by a helmet-to-helmet hit by Jonathan Jones in the opening minute of the fourth quarter. Allen was briefly evaluated under a tent on the sideline before being escorted up the tunnel.
The game wasn't decided until Buffalo's final drive with Barkley facing third-and-9 at the New England 39.
Linebacker Kyle Van Noy applied the pressure by driving in from Barkley's right, and got a hand on the quarterback's chest. Barkley's follow-through was affected causing the ball to pop into the air, which Collins easily secured.
Though Tom Brady didn't play much of a factor, he upped his career record to 31-3 against Buffalo — extending the NFL career mark for most victories by a quarterback against one opponent. New England won its sixth straight against the Bills, and improved to 34-5 against Buffalo since the start of the 2000 season.
Scoring didn't come easy in a game in which the teams combined for 14 punts.
Another key Patriots stop came on the drive Allen was hurt. With Buffalo facing fourth-and-goal from the 2, Barkley threw a high pass that glanced off receiver Zay Jones' fingertips five minutes into the fourth quarter.
New England's 16 points all came off Bills turnovers.
Bolden scored after Allen threw his first interception. He was picked off by Devin McCourty after forcing a pass deep over the middle into double coverage.
Two series later, the Patriots went up 13-0 when Jackson was untouched coming off the right side to block Corey Bojorquez's punt. The ball bounced into the hands of Slater, who ran in untouched.
New England was on the verge of running away with the game before Brady threw an interception facing third-and-goal from the 2 with under five minutes left in the second quarter. His pass intended for Julian Edelman was picked off by safety Micah Hyde.
Brady was held in check in being limited to 18 of 39 for 150 yards and an interception.
The Patriots were held under 30 points for the first time this season. They allowed their first points in the first half this season on Stephen Hauschka's 46-yard field goal with 1:55 left in the second quarter. And New England then gave up its first offensive touchdown of the year when Allen capped Buffalo's first drive of the second half with a 1-yard dive over the middle on fourth down.
Patriots kicker Stephen Gostkowski hit a 23-yard field-goal attempt, but was wide right on his first of two extra-point attempts.
The Bills' defense did its part in the first half by limiting Brady to 9 of 22 for 90 yards and an interception. It was Brady's lowest completion percentage in the first half since he went 7 for 19 in a 27-26 win over Cleveland on Dec. 8, 2013.
Brady has struggled in his previous four games against Buffalo, coinciding with the arrival of Bills' defensive-minded head coach Sean McDermott and coordinator Leslie Frazier. He entered the game averaging just 232 yards passing per outing with a combined three touchdowns and four interceptions.
Allen finished 13 of 28 for 153 yards and three interceptions. Barkley went 9 of 16 for 127 yards and an interception.
Running back Frank Gore led Buffalo with 109 yards rushing, and in the process became the fourth player in NFL history to top 15,000 yards rushing. The 36-year-old entered the game needing 88 yards.