Shoni Schimmel came off the bench to contribute 15 points and six assists for the Cardinals (23-6, 11-4), playing their final regular-season home game. Louisville has won nine of its past 11 games.
Seton Hall was only seven back at 51-44 on Alexis Brown's 3-pointer with 11:02 left, then Louisville began pulling away. Cortnee Wanton's free throw made it 60-46 with 6:28 remaining, and Schimmel was 6 of 6 from the line in the last 45 seconds to seal it.
Brittany Morris scored 20 points, Ka-Deidre Simmons had 18 and Brown 14 for the Pirates (9-19, 4-11), who have lost seven of their past eight games.
Louisville shot 20 of 40, 8 of 14 on 3-pointers and 24 of 30 from the foul line.