Notre Dame's Pat Connaughton sank one of two free throws with 26 seconds left in regulation to force the extra session, and the Irish outscored South Florida 12-8 in the additional five minutes.
The game was all but sealed when South Florida, trailing by two at the time, threw away an inbounds pass with 1.0 seconds remaining. Connaughton provided the final margin with two free throws.
South Florida pushed ahead early in the first half, seizing a 20-8 lead, but the rest of the half was Notre Dame's. The Fighting Irish scored the next 18 points and entered intermission with a 28-26 advantage.
Connaughton and Jerian Grant paced Notre Dame with 12 points apiece.
Victor Rudd Jr. scored 16 points with seven rebounds for South Florida, while Anthony Collins added 13 points and seven assists.