Bonzie Colson had his sixth straight double-double with 17 points and 14 rebounds, and Steve Vasturia scored 21 points for the Fighting Irish (9-0). They are off to their fastest start in coach Mike Brey's 17 seasons — and the school's best since opening 12-0 in 1973.
"We handled our business," Brey said. "I thought we were poised and knew we weren't going to get beat. We just kind of adjusted and figured it out."
Fort Wayne used a 20-5 run to get within single digits with 2:48 to go after Charles Ruise Jr.'s one-handed floater in the lane.
Four straight free throws by Matt Farrell, including a pair following a technical foul on Fort Wayne coach John Coffman, helped seal it for Notre Dame.
"We knew they were going to have their run," Colson said. "We just stayed composed and stayed together."
Fort Wayne native V.J. Beachem added 14 points, Farrell had 12 and Colson hit a career-high three 3-pointers.
"He's a special guy," Brey said of Colson. "He just is really confident and growing. Some of the stuff he's doing outside the arc, step-back 3s, stepping up. I just want to let him keep blossoming."
Mo Evans scored 21 of his 25 points in the second half to lead Fort Wayne (7-3), which had won six straight — including an upset of then-No. 3 Indiana in overtime. John Konchar added a season-high 18 points to go with nine rebounds for the Mastodons.
Bryson Scott, who came in averaging 16.9 points and was shooting better than 62 percent from the floor over his last six games, missed all 10 of his field goal attempts and finished with two points.
"That is a really stingy defense that sits in gaps and really makes you work to get good shots," Coffman said. "I don't think we put our best attack and toughness out there on the floor."
Seldom-used reserve John Mooney's put-back dunk with a second left gave the Irish a 41-23 lead at the break, the fewest points Notre Dame has allowed in the first half this season.
A 10-2 Irish run over the first 4 minutes of the second half pushed their lead to 27.
In a matchup of the nation's No. 10 scoring offense (Notre Dame at 89.1 points per game) and No. 11 scoring offense (Fort Wayne at 88.7 ppg), it was the Irish defense that gave the Mastodons fits early.
Fort Wayne entered ninth in the country in field goal percentage, but started cold, hitting just four of its first 15 shots while the Irish built a 14-point lead 12 minutes into the game.
"I just think our focus level wasn't where it should have been," Evans said. "We came out and we dug ourselves a hole."
The Mastodons made only one of their first 14 tries from 3-point range, but shot 58 percent from the field in the second half to fuel their comeback.
The Irish will have a chance to make a major rise over the next two weeks, with ranked teams Villanova and Purdue coming up on the schedule. Fort Wayne received one vote this week, but likely won't factor into next week's poll.
Martinas Geben's missed free throw early in the second half snapped a string of 31 straight makes from the foul line for Notre Dame. The Irish, who came in leading the country in free throw shooting at 85.8 percent, finished 20 of 23 from the line.
"It's definitely a weapon," Vasturia said. "It's been a great advantage for us to get in the bonus early."
Fort Wayne: Was the win over Indiana on Nov. 22 just a fluke? After crashing back to reality against Notre Dame, the Mastodons will try to right the ship in their final three non-conference games before Summit League play starts.
Notre Dame: The Irish, the last undefeated team left in the ACC, did what the Hoosiers could not in putting away Fort Wayne. Now, Notre Dame heads into its big matchup against No. 1 Villanova with plenty of momentum.
Fort Wayne: Before beginning a stretch of eight days between games, the Mastodons return home Saturday to face Austin Peay, a team they already beat once this season, 103-99 in Clarksville, Tennessee.
Notre Dame: The Irish face their toughest stretch of the season to date, heading to Newark, New Jersey, to meet No. 1 Villanova on Saturday, followed by a matchup in Indianapolis with No. 18 Purdue a week later.