Chris Dominguez hit two of Louisville's four home runs.
Justin Marks allowed two singles before taking a hard shot to his left leg, and the Cardinals eliminated Mississippi State from the College World Series with a 12-4 victory Sunday.
Louisville's powerful offense kept the Cardinals (47-23) alive in their first CWS appearance. They play Tuesday against the loser of Sunday night's Rice-North Carolina game.
Mississippi State (38-22) went two games and out for the first time in seven CWS appearances since the 1971 Bulldogs went winless here.
The Cardinals found themselves fighting for survival after squandering leads of 5-0 and 10-4 in Friday's 15-10 loss to Rice.
Sunday, the Cards broke out to an 8-0 lead, and they didn't fold this time.
After Mississippi State scored three runs in the bottom of the sixth, Louisville came back with three in the seventh, highlighted by Dominguez's two-run shot to left.