Brady threw for 252 yards to pace New England (2-1) to its 14th straight win over Buffalo. New England hasn't lost to the Bills since the first week of the 2003 season.
BenJarvus Green-Ellis ran the ball 16 times for 98 yards and a score. The Patriots also got a rushing touchdown from Danny Woodhead and Rob Gronkowski contributed a TD reception.
Buffalo (0-3) got a 95-yard kickoff return and a TD reception from C.J. Spiller. Quarterback Ryan Fitzpatrick went 20-of-28 passing for 247 yards, two touchdowns and two interceptions.
Steve Johnson hauled down a touchdown pass and Marshawn Lynch piled up 79 rushing yards on 13 attempts.