Desperately needing a win to enhance their NCAA resume, the host Bearcats never trailed the No. 16 Cardinals, handing Rick Pitino's team a 63-54 loss.
Cincinnati guards Sean Kilpatrick and Cashmere Wright combined for 38 points to lead the Bearcats. Wright, a sophomore, finished with a game-high 20 points, while Kilpatrick, a freshman, chipped in 18.
Though Louisville held their own on the boards - UC out-rebounded the Cardinals 26-25 - Cincinnati's tough, aggressive perimeter defense proved the difference in the game.
After making 13 three's against Syracuse last Saturday, Louisville made just 4-17 three's against Cincinnati. Cincinnati also had 12 steals, forcing 15 UofL turnovers.
The Bearcats opened an 18-6 lead midway through the first half, and led 36-24 at halftime. UofL never cut Cincinnati's lead under five points in the last nine minutes of the opening half.
Cincinnati increased their lead to 15 on a three-pointer right out the break, then made it 41-26 on Wright's basket with 19:09 remaining.
Louisville cut the lead to 43-38 on Kyle Kuric's layup with 13:20 but never got closer. Cincinnati scored the next seven points as Rashad Bishop, Kilpatrick and Dion Dixon delivered field goals and Yancy Gates made 1 of 2 free throws as the Bearcats opened a 50-38 lead with 9:51 remaining.
UofL scored just four field goals in the final 9:30 of the game.
Terrence Jennings led UofL with 12 points. Preston Knowles added 11.