Louisville took a 19-point lead at halftime on the way to a win that kept the Cardinals within reach of Cincinnati at the top of the American Athletic Conference.
The Cardinals shot 56 percent from the field and suffered only nine turnovers. Smith added six assists while both Luke Hancock and Montrezl Harrell had 15 points. Chris Jones added 14.
Louisville is 19-4 for the season and is 8-2 in conference play. Cincinnati is atop the league standings at 10-0.
Both TaShawn Thomas and Jherrod Stiggers scored 14 points for the Cougars (11-12, 3-7 AAC), who have lost five in a row and seven out of eight.