Louisville rallied from 17 points down in the second half and took a 64-61 lead on a three-pointer by Russ Smith with 5:01 left.
But the Cardinals couldn't hang on.
Cincinnati outscored the Cardinals 8-2 to end the game and snag a 69-66 victory at the KFC Yum! Center on Thursday night.
"You give them a lot of credit because they lost total momentum in the game and good defensive teams can come back and hold on," U of L coach Rick Pitino said. "We made a couple of really big blunders down the stretch."
The Cardinals still led 64-63 when Justin Jackson got free on the offensive glass and scored on a tip in. U of L then turned the ball over and Russ Smith missed a layup.
The Cardinals then failed to foul the right guy, sending Sean Kilpatrick - who was 11-for-11 - to the line to hit four in the final seconds and seal the deal for Cincy (20-2, 9-0).
Louisville drops to 17-4, 6-2 in AAC play. Montrel Harrell led the team with 18 points and six rebounds, while Russ Smith and Luke Hancock scored 16 points apiece.
Check back on this story for more updates on the game from Cardinal Authority: