Natalie Novosel's jumper as time expired 54 victory over No. 7 Duke in the Junkanoo Jam Freeport Division championship game.
Novosel finished with 15 points and Skylar Diggins scored a game-high 19 for Notre Dame (5-1), which trailed 36-20 at the half.
Elizabeth Williams paced Duke (4-1) with 16 points and 13 rebounds while Chelsea Gray scored 11 points for the Blue Devils.
After being held to just 23 percent shooting in the first half, Notre Dame came out on fire in the second.
Duke's Haley Peters opened the second half with a layup to extend the Blue Devils' lead to 38-20, but for the next 10 minutes it was all Notre Dame as the Irish ran off a 21-3 spurt to knot the game at 41 with 9:24 left in regulation.
Duke missed five shots and turned the ball over seven times in that span.
Neither team would lead by more than four points for the remainder of the game and Duke took a three-point lead into the final 1:35 of regulation.
Diggins then missed a three but got her own rebound, leading a missed trey by Kayla McBride and another by Diggins as Notre Dame kept getting offensive rebounds.
McBride was fouled and made 1-of-2 free throws to bring the Irish within 54-52 with 53 seconds to go.
A Diggins layup then tied the game and after Duke's Shay Selby failed to find the bottom of the net, Novosel banked a shot in from the foul line as the buzzer sounded to cap the comeback.