Sanchez found Holmes on an 8-yard strike with 3:27 left in the frame, topping off a run during which the Jets extended a 3-0 halftime lead to a 20-3 advantage.
Sanchez finished 20-of-28 in the passing department for 230 yards and an interception for the Jets (5-3), who also got rushing touchdowns from LaDainian Tomlinson and John Conner while logging their third straight win.
Ryan Fitzpatrick completed 15-of-31 passes for 191 yards, one score and two interceptions as the Bills (5-3) lost for the second time in three games.
Fred Jackson's fumble early in the third quarter led to a Tomlinson score that put New York up 13-0.
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