Natalie Novosel netted a career-high 32 high 18 rebounds as season school record for wins by downing South 68, on Saturday.
Skylar Diggins had 18 points for the Irish (27-2, 14-1 Big East), who clinched at least a share of the Big East regular season title. The Irish wrap up the regular season on Monday against Connecticut, which is a game back in the conference. Notre Dame has won three straight since falling to West Virginia on February 12.
Inga Orekhova and Jasmine Wynne each scored 18 points for South Florida (15-14, 7-8), which had its three-game winning streak snapped.
Andrell Smith's layup gave the Bulls a 44-41 lead early in the second half, but Novosel provided the lift for the Irish down the stretch.
Up by three, 61-58, Novosel scored nine points during a 13-4 run to put the game away as Notre Dame led, 76-64, with under two minutes to play.
The Irish shot 46.4 percent in the opening half en route to a 41-38 halftime advantage.