Skal Labissiere added 17 points for the Wildcats (6-0), who led by as many as 31. Charles Matthews scored 11 points and Isaiah Briscoe finished with seven assists for Kentucky, now a winner of 37 consecutive regular-season games and 39 in a row against unranked opponents.
Chris Perry scored 14 points for USF (1-5), which has lost 18 consecutive games against teams ranked in the Top 25. Jaleel Cousins added 12 points on 5-for-6 shooting, and Jahmal McMurray scored 11 points for the Bulls.
Kentucky played the second half without starting guard Tyler Ulis, who departed with a right elbow injury after getting hurt while fighting for a ball loose on the floor.