The Bills gave up an early score, then answered with three first-half touchdown drives to beat the Giants 28-to-14.
Bills safety Jordan Poyer had an interception to help seal the win.
He says when the offense is driving for touchdowns, it provides motivation for the defense. And defensive tackle Harrison Phillips says the Bills are maturing as a football squad.
The Bills are 2-and-0 for the first time since 2014. The Giants are 0-and-2 for the sixth time in the last seven seasons.
The Bills play their home opener next Sunday against Cinicinnati.