Louisville (17-5) lost for the fourth time in its last five games, turning in an uninspired performance on both ends of the court.
Texas Christian (10-12) never trailed and built a 33-18 lead by halftime. The closest Louisville got in the second half was nine points.
Chudi Chinweze's layup on the fast break started a 14-0 tear to open a 61-37 lead with 5:36 left to play. Nucleus Smith scored seven points and Santee the other five in the spurt.
The Cardinals were held without a point for more than five minutes during that span. Coach Rick Pitino tried calling a pair of timeouts, but nothing was able to wake his club.