Unlike Saturday when the Irish needed five overtimes to finally top Louisville, they only needed one against DePaul.
"That's really as big a win as Saturday, when you turn around and dig one out when it doesn't look good at times," Notre Dame coach Mike Brey said.
Jerian Grant scored 21 points, including a big three-point play in overtime, to lift the Irish (20-5, 8-4 Big East). Grant, who scored 12 points in the final minute of regulation against Louisville, came up big in overtime this time.
Pat Connaughton hit a 3-pointer to give the Irish a 74-70 lead . After Brandon Young hit a 3-pointer to cut the lead to one-point, Grant got the rebound of a miss by Atkins and scored, then made free throw and the Irish made 5-of-6 free throws in the final 21 second to hang on.
"It is tough," said Cleveland Melvin, who led DePaul with 23 points. "We were fighting the entire second half, but it is tough to get over the hump in overtime."
The Irish needed to overcome 10 turnovers and 39 percent shooting in the second half as they appeared to run out of energy.
"We turned the ball over a little bit. They got some easy buckets. They just started hitting their shots," said Notre Dame guard Eric Atkins, who had 13 points and nine assists.
The Irish weren't helped by a lethargic crowd of 8,554, with less than half of the student section filled.
"I feel like going into the dorms and chasing some of my students down," Brey said. "I thought we deserved a little more from our legion given the show we gave them Saturday night."
Grant said it was a tough game coming off the game against Louisville.
"We could have been tired and just said we'll let one get away, but for this team to come back and go into another overtime and pull it out is definitely mentally tough," he said.
The Irish improved to 3-1 in overtime games this season and played back-to-back overtime games for the first time since 1999-2000.
"Their record won't say it, but they're a good team and they can score the ball," Grant said.
Brandon Young added 20 and Donavan Kirk added 16 as DePaul lost its ninth straight.
DePaul coach Oliver Purnell was encouraged the Blue Demons gave the Irish a better challenge than it did on Feb. 2, when they lost 79-71.
"I'm not happy with it. I'm encouraged our guys continue fight and continue to get ready," he said.
Jack Cooley, who had 11 points for the Irish, said the Irish learned something with the victory.
"We have learned that we are in great shape and that we can play through being tired," he said.