The Gamecocks (33-23) advance to play third-seeded Kentucky on Wednesday with the format moving to double elimination. The Commodores (33-22-1) are eliminated.
South Carolina capitalized on three walks and doubles by Justin Row and Destino in the top of the 11th.
Carlos Cortes and Jonah Bride both homered in the first two innings for South Carolina. Cortes drew four walks in the game, including an intentional pass in the 11th.
Vandy's Will Toffey had a three-run double in the second inning and the Commodores tied it 4-4 on Connor Kaiser's seventh-inning homer.
South Carolina reliever Tyler Johnson (1-2) pitched 4-1/3 scoreless innings.