Nolan Cressler scored 17 points and Robert Hatter had 15 to pace Cornell, which has now lost 15 in a row dating back to last season, one away from tying the school record longest losing streak of 16, set in the 1972-73 season.
The Big Red, which won 29 games and advanced to the Sweet 16 in 2010, is 0-9 for the first time since 1904-05, when it started 0-10.
After starting the game 2-for-10, Notre Dame (5-1) found the range and finished with its highest point total of the season. The Irish broke the 100-point mark for the first time since its 5-overtime upset of Louisville last season.
Grant knocked down a pair of 3-pointers early in the second half as Notre Dame hit four in a row from deep, but Hatter kept the Big Red within striking distance. Hatter scored Cornell's first six points of the second half and continually found room in the lane, forcing Notre Dame coach Mike Brey to switch to a zone defense.
Cornell missed its next three field goals and a 3-pointer. A three-point play by Connaughton started a 17-2 run that pushed Notre Dame's lead to 25 points with 6:26 to play.
Cornell went 4:29 without a field goal during that run. Grant's three-point play with 7:18 remaining got him to the 1,000-point mark.
Freshman guard Demetrius Jackson earned his first career start as the Irish went with a three-guard lineup against the perimeter-oriented Big Red, who average just over 26 3-point attempts per game.
Cornell, which finished 8 of 21 from the arc, hit its first two 3-pointers and scored the game's first eight points before the Irish got it going. Notre Dame scored the next 10 points, and went on a 22-4 run to go up by 10 with 8:39 to play in the first half. Cornell hit just 1 of 11 shots, including seven straight misses, during that nine-minute stretch.
Notre Dame's biggest first-half lead was 14 points, and Connaughton finished the half with 12.