Anthony Davis added 18 for the Wildcats (13-1), including four clutch free throws to help stave off a furious Louisville (12-2, 0-1 Big East) rally in which Russ Smith scored 8 points in the final 12 seconds.
Smith came off the bench to log 28 minutes of playing time and lead the Cardinals with 30 points. He was the only Louisville player in double figures.
Louisville shot 32.3 percent from the field, but that was better than the Wildcats, who went 17-of-57 from the field for 29.8 percent.
The Wildcats led 36-33 at halftime but Louisville chipped away ever so slowly until Smith hit a 3-point bucket with 15:23 to play to cut Kentucky's lead to 40-39. Kentucky later put together a 10-4 run that gave them a 61-50 lead with 3:41 to play.