Natalie Novosel scored 21 points and Skylar 59 win over No. 4 Connecticut at XL Center.
The Fighting Irish (28-2, 15-1 Big East) forced 18 turnovers and had 25 second-chance points to upend UConn for the third straight time.
The Huskies (26-4, 13-3) have now dropped two in a row at home after having their 99-game home winning streak snapped by Saint John's on February 18.
Tiffany Hayes paced UConn with 22 points, while Stefanie Dolson netted 18 in the loss. The Huskies had not lost three Big East regular season games since the 2004-05 season.
The Irish, who led 38-35 at halftime, held the Huskies without a point over the final 7 1/2 minutes, finishing the game on a 9-0 run.
Diggins and Brittany Mallory made consecutive three-pointers during the flurry for a 69-59 advantage with five minutes left, and Notre Dame never looked back in posting a new school record with its 10th win over a ranked opponent.
Notre Dame will be the No. 1 seed in the Big East Tournament, while the Huskies will be seeded third.