The Irish (8-1) scored 65 points in the first half and built a 26-point lead. They did it by shooting 76.5 percent from the field ( 26 of 34), including 8 of 11 from 3-point range.
DePaul (6-3) used a 19-5 run in the third quarter to get back into the game. Chanise Jenkins led the Blue Demons with 21 points and Jessica January added 17.
Notre Dame faced its third straight ranked opponent and has now won eight straight against the Blue Demons.