Nassib completed 15-of-23 passes for 246 yards for the Orange (5-5, 4-2 Big East) and Prince-Tyson Gulley ran for two scored to snap a three-game losing streak. Gulley ran for 98 yards and scored twice in the first half to give Syracuse a 31-13 lead at halftime.
Syracuse scored three touchdowns in the second quarter and limited the Cardinals (9-1, 4-1) to a field goal in the closing seconds of the period.
Jerome Smith ran for 144 yards and a touchdown for Louisville. Teddy Bridgewater completed 36-of-50 passes for 422 yards and three touchdowns for the Cardinals, who gained only 48 yards on the ground and committed two turnovers.