Dan Marino threw three touchdown passes as second-ranked Pittsburgh overcame six turnovers and an early 10-0 deficit to extend its winning streak to 13 games, longest in the nation.
Syracuse (1-5-1) led the host Panthers, 10-0, late in the first period on a 36-yard field goal by Gary Anderson, his ninth straight successful attempt, and Joe Morris' seven-yard scoring run.
But Pitt (6-0) took the lead for good with 17 points in the second period.
After Snuffy Everett kicked a 32-yard field goal, Marino followed on the next series with a 13-yard touchdown pass to tight end John Brown to give Pitt a 10-10 tie with 3:54 left in the half.
With about a minute left in the half, Pitt cornerback Dan Short intercepted a pass by Dave Warner at the visitors' 22-yard line. Marino threw a two-yard touchdown pass to wide receiver Julius Dawkins with 15 seconds left before halftime.
Marino finished with 27 completions in 41 attempts for 282 yards. He had four interceptions.
Morris finished with 128 yards rushing on 31 carries against a Pitt defense that had been allowing an average of 18 net rushing yards a game.