A month ago, Muffet's Squad was left with a bitter taste in their mouths when they were unable to get a shot off in the final seconds and lost at home to DePaul by a point.
Sunday, it was a similar situation with DePaul unable to get a shot off in the final seconds as Notre Dame won in Chicago for the first time since 1991, 66-64.
It was the 5th win in six games for the Irish, who are now 9-4 in the Big East and 21-6 overall.
The win was huge for Notre Dame which takes over sole possession of 4th place in the Big East standings. A loss would have put the Irish in a 5-way tie for 4th.
The top four teams in the conference standings get a bye in the Big East Tournament.
Erica Williamson scored a career-high 16 points and added 8 rebounds to lead the Irish.
Charel Allen scored 12 points and Lindsay Schrader had 11.
Notre Dame led 39-32 at halftime but saw the lead quickly vanish as Allie Quigley capped off a 9-0 run to give DePaul the lead. Quigley led all scores with 21.
Both teams traded the lead throughout the 2nd half, but the Irish would build a 5-point advantage with 1:20 to go on an Allen jumper.
After Allen missed one of two free throws with 11.5 seconds left, DePaul trailed by just two.
Guard China Threatt had an open look to the basket but kicked it out at the last seconds perhaps thinking the Blue Demons needed a three. DePaul would never get the shot off as Brittany Mallory came up with a big deflection to end the game.
Notre Dame finishes its road trip winning two of three games.
They return to the Joyce Center on Wednesday to host South Florida.