The Bearcats won its 13th straight game, reached 20 victories for the season, stayed unbeaten in the American Athletic Conference, and posted one of the biggest results of the college basketball campaign by defeating the defending NCAA champions on their court.
Cincinnati owned a seven-point lead as the game headed into its final 10 minutes, but Louisville went on a 14-4 run and moved in front by three with 5:30 to go.
The Bearcats then regained their poise against one of the strongest defensive teams in the country and closed the contest on an 8-2 surge.
Kilpatrick scored 10 of Cincinnati's last 12 points and he finished with 28. His two free throws with nine seconds left put the Bearcats in front by three, after which Terry Rozier made two foul shots for Louisville with six seconds remaining.
Kilpatrick again went to the foul line with five seconds to play and he hit two more shots to account for the final score. A 3-point attempt at the buzzer by Louisville's Luke Hancock failed to reach the rim.
Justin Jackson and Shaquille Thomas both had 11 points for Cincinnati (20-2, 9-0 AAC).
Louisville (17-4, 6-2 AAC) was led by Montrezl Harrell with 18 points. The Cardinals forced 20 turnovers, but were outrebounded by 10 and made just 6-of-21 from 3-point range.