Louisville appeared on its way to advancing to Thursday's quarterfinals when Edgar Sosa drained an outside shot to give Louisville a 46-34 lead early in the second half.
Then Samardo Samuels went to the bench with his third foul and Cincinnati went to work on a comeback.
With Samuels on the bench, the Bearcats went on an 11-0 run over the next four minutes. Sosa committed two turnovers and threw up a wild, driving layup during the stretch.
Cincinnati opened a seven point lead at 60-53 when Jaquon Parker converted an old fashion, three-point play with 6:22 remaining.
Louisville closed the gap to 64-63 with 1:45 but Sosa missed the potential tying free throw. He made only 3 of 8 free throws against the Bearcats.
Lance Stephenson connected on a pair of free throws to push the Bearcats lead to 67-63 with :26 remaining.
Reginald Delk cut the margin to one, 67-66, with nine seconds remaining on his fourth three-pointer of the game.
Louisville quickly fouled and Vaughn made two free throws for the final margin.
Sosa tried to attempt a last second shot to send the game to overtime but Vaughn knocked the ball loose before Sosa could get the shot off.
Yancy Gates led Cincinnati with 16 points. He also had six rebounds to help the Bearcats win the rebounding war 46-29.
Sosa led Louisville with 28 points.
The Cardinals, 20-12, now wait to see what their NCAA Tournament fate will be.