Syracuse (1-4, 0-1 Big East) opened the scoring with a 28-yard field goal by Collin Barber before Pittsburgh erupted for 48 straight points. Rutherford found Larry Fitzgerald for a 27-yard touchdown and Miree scored from six yards and one yard out as the Panthers built a 24-3 halftime cushion.
Fullback Lousaka Polite scored on a 34-yard run to open the scoring in the second half, linebacker Lewis Moore returned a fumble two yards for a score and Rutherford hit Roosevelt Bynes on an 82-yard catch-and-run touchdown to give the Panthers a 48-3 cushion with just under six minutes left in the third quarter.
Pittsburgh (5-1, 2-0) defeated Syracuse for the first time since 1989 and won at the Carrier Dome for the first time since 1982.
Polite gained 58 yards on five carries for Pittsburgh, which rushed for 180 yards and outgained the Orangemen in total offense, 459 yards to 275.
David Tyree hauled in a four-yard pass from Troy Nunes for Syracuse's first touchdown that ended Pitt's 48-point run with just over three minutes left in the third quarter. The Orangemen added a pair of meaningless scores in the fourth.