DeVante Parker and Dominique Brown scored touchdowns to help No. 21 Louisville hold off Memphis 24-17 on Saturday.
The Cardinals used a 17-point surge over the second and third quarters to provide a cushion.
Louisville seemed in control leading 24-3 before quarterback Paxton Lynch rallied Memphis within seven points with a 4-yard run early in the fourth quarter and a 6-yard TD pass to Jesse Milleson with 6:07 remaining.
The Tigers' defense was poised to give Lynch another opportunity but Reggis Ball was penalized for roughing punter Ryan Johnson, giving the Cardinals first down at the Memphis 29 with 2:58 left.
Louisville (10-1, 6-1 American Athletic Conference) eventually turned it over on downs at the Memphis 6. But with no timeouts left, the Tigers (3-7, 1-5) gained just 17 yards before time expired.
The Cardinals registered their first senior day win since 2007.