Smith drained 6-of-10 3-point attempts and Luke Hancock added 16 points as the Cardinals (12-2, 1-0 AAC) shook off a loss to No. 16 Kentucky Sunday and this week's dismissal of forward Chane Behanan for off-court behavior.
Louisville was in command throughout after opening the game with a 15-2 run.
Montrezl Harris supplied 15 points and eight rebounds.
Isaiah Sykes had 16 points and eight rebounds for the Knights (8-4, 0-1).