Devereaux Peters and Natalie Novosel both 54 Big East Tournament quarterfinal win over DePaul.
Peters added 12 rebounds while Kayla McBride finished with 14 points for the Fighting Irish (29-2), who advanced to play West Virginia in Monday's semifinal.
Katherine Harry scored 14 points to pace eight-seeded DePaul (22-10). Jasmine Penny chipped in 10.
Notre Dame led 22-19 near the midway point of the first half before opening up a double-digit advantage with a 12-5 run.
McBride hit a three-pointer during the stretch and Peters capped it with a layup, making it 34-24.
The Irish were still up 10 when Skylar Diggins connected on a layup for a 38-26 lead at the break.
They opened the second half with 10 straight points to put the game away.
McBride started with a three-pointer and Novosel scored five in a row to make it 48-26. Notre Dame wasn't threatened the rest of the way.