The Cardinals finished the year with a trip to the NCAA Sweet 16.
Russ Smith's 18-foot jumper with 2.2 seconds was the game-winner for the Cardinals.
Wayne Blackshear scored 16 points for the Cardinals.
The two programs last met in 1987 in Hawaii in the Rainbow Classic.
Russ Smith scored a game-high 19 points.
Louisville v Kentucky | NCAA Regional Semifinal
NCAA Regionals | Practice Day 1
USATSI gallery, NCAA men's basketball tournament
Louisville Men's Basketball v Saint Louis | NCAA Round 3
Louisville v Manhattan | NCAA Round 2