The Wildcats, led by freshman Jodie Meeks' 18 points, knocked off the Cards for the third straight season.
Louisville couldn't find the basket against Kentucky , shooting just 27 percent from the floor for the game. The Cardinals were 3-24 from three-point range.
"This is kind of a scary thought, but that's probably the best we've run our offense the whole year," said Rick Pitino, who fell to Tubby Smith for the fourth time in six seasons at Louisville. "It's an obvious thing we're not a good shooting team."
For the second year in a row, Rick Pitino's team has dropped back-to-back home games. The Cards fell to UMass 72-68 Wednesday night at home.
Louisville out-rebounded Kentucky 44-40, getting a game-high 10 boards from junior David Padgett, but the Cardinals couldn't capitalize even though the Wildcats starting frontcourt of Randolph Morris and Bobby Perry combined for only 2 points and five rebounds.
Padgett led Louisville with 16 points. Junior forward Juan Palacios was the only other Cardinal to score double-figures. Palacios had 10 points.
Two telling statistics for the Cardinals. Kentucky out-scored Louisville 10-0 on fast-break points and the Wildcats bench had 22 more points than Louisville's.