The Bills totaled 408 yards of offense and never trailed, but didn't put the game away until late in head coach Sean McDermott's debut.
LeSean McCoy led the Bills with 159 total yards (110 rushing, 49 receiving). McCoy left the game briefly in the fourth quarter with a wrist injury, but was able to return.
Safeties Jordan Poyer and Micah Hyde each made fourth-quarter interceptions in their debuts for Buffalo.
Mike Tolbert's 1-yard touchdown plunge gave the Bills a two-touchdown lead with 12:47 remaining. A 22-yard reception by Nick O'Leary put the Bills in scoring range.
The Jets started a drive at the Buffalo 39 after a 36-yard punt return by Kalif Raymond with under eight minutes remaining, but Poyer intercepted McCown three downs later to foil the scoring chance.
Hyde's interception with 1:35 remaining sealed the Bills win.
The stripped-down Jets struggled to sustain drives until late in the third quarter when McCown led an 11-play, 75-yard march that culminated with his 1-yard touchdown run on fourth down. McCown's attempt at a tying 2-point conversion pass was intercepted by Buffalo's Ramon Humber.
Buffalo held a 236-85 advantage in yardage at halftime, but only led 7-6. McCoy himself gained more total yards (96) in the first half than the Jets.
Charles Clay caught a 1-yard touchdown pass from Taylor to give the Bills a 7-0 lead early in the second quarter.
On the Bills' opening drive, Clay had a potential touchdown pass bounce off his hands and get intercepted by New York's Juston Burris.
Chandler Catanzaro kicked field goals from 52 and 48 yards in the second quarter for the Jets. Buffalo's Stephen Hauschka missed a 46-yard attempt.
NOTES: The Bills recognized the 25th anniversary of their NFL record comeback victory over the Houston Oilers on Jan. 3, 1993 in a halftime ceremony. Hall of Fame members Jim Kelly, Thurman Thomas and Andre Reed were among the 25 former players in attendance. ... Jets QB Bryce Petty (knee) participated in warmups, but was inactive. Christian Hackenberg backed up McCown. ... Bills CB E.J. Gaines (shoulder), Jets TE Eric Tomlinson (elbow), and Jets LB Bruce Carter (ankle) left the game with injuries. ... The Jets beat the Bills twice last season.