Joey Pankake drove in two runs during a five-run second inning for the Gamecocks (43-19), who forced a decisive game Monday in the best-of-3 series with the winner going to the College World Series.
The Tar Heels (56-10) won Saturday's opener 6-5 on an RBI single in the ninth, putting them within a win of returning to Omaha, Neb., for the sixth time in eight seasons.
But the No. 1 overall seed in the NCAA tournament got a short outing from a starting pitcher and fell behind early for the second straight day.
Landon Lassiter had two hits for the Tar Heels, who will be the home team in Monday's deciding game three.