The Cardinals, who trailed by one at the half, were led by Russ Smith and Luke Hancock, who scored 21 and 20 points respectively.
Chane Behanan, who had 10 second half points, led the top-seeded Cardinals with nine rebounds.
Louisville struggled from the floor throughout, but forced seven second half turnovers to fuel their game-winning run.
Will will face the winner of the Michigan - Syracuse contest for the NCAA Championship on Monday night in Atlanta.
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