Joe Jackson and Shaq Goodwin each scored 15 points and Memphis rallied late for a 73-67 upset of the 12th-ranked Cardinals.
Geron Johnson added 13 points, Chris Crawford 12 and Austin Nichols 10 as all five starters scored in double figures to help the Tigers end a four-game losing streak to the defending national champions.
Memphis (11-3, 2-1 American Athletic Conference) shot 51 percent (28 of 55) and outrebounded the Cardinals 37-35 in a victory that almost slipped away in the second half.
Luke Hancock had a season-high 20 points to lead Louisville (13-3, 2-1).