Pitt quarterback Tino Sunseri was 25-of-33 passing for 319 yards with Devin Street catching 10 passes for 130 yards.
The Orange defense, strong throughout the game, was led by Brandon Sharpe's career-high seven tackles including six for a loss and four sacks.
After the Orange defense forced a three-and-out on Pitt's first possession of the game, the offense marched 80 yards on 11 plays, capped off by an Adonis Ameen-Moore one-yard touchdown run, giving Syracuse a 7-0 lead with 9:54 left in the first quarter. Nassib was 4-of-4 passing for 51 yards on drive, Syracuse's first opening drive resulting in a touchdown this season.
On Pitt's next possession, the Syracuse defense came up with a key stop on 3rd-and-3 at the SU 23, stopping Ray Graham for a loss of two. Kevin Harper's ensuing 42-yard field goal attempt missed wide right, keeping it 7-0 with 4:54 remaining in the opening quarter.
Dyshawn Davis' 52-yard fumble return for a touchdown staked Syracuse to a 14-0 lead with 1:06 left in the first quarter. The linebacker scooped up Drew Carswell's fumble and took it the distance behind a convoy of blockers after the tight end was stripped by Jeremi Wilkes following a short reception at the Orange 48-yard line.
Pitt drew within seven early in the second quarter on a Ray Graham one-yard touchdown run, capping off a 12-play, 62-yard drive that used 5:25, cutting the Orange lead to 14-7 with 10:41 remaining in the opening half.
Syracuse looked poised to add to the lead late in the half after picking up a 4th-and-9 at the Pitt 33-yard line, taking the ball down to the nine, but K'Waun Williams intercepted Nassib's pass intended for Sales in the end zone with 5:19 left in the second quarter.
Kevin Harper's 40-yard field goal for Pitt with 22 seconds left in the first half made it a 14-10 game when the teams went to the locker rooms.
In the third quarter, Pitt added a 27-yard field goal with just under two minutes left, but the Syracuse defense stood strong in the fourth quarter, stopping all of Pittsburgh's offensive possessions.
After forcing a Pitt punt and taking over with 4:54 remaining, the Orange picked up four critical first downs, led by rugged running by Ameen-Moore to run out the clock and clinch SU's first victory over the Panthers since 2004.
Syracuse continues BIG EAST play next week against Rutgers. Kickoff against the Scarlet Knights is slated for 12 p.m. Saturday, Oct. 13 at High Point Solutions Stadium.