Keisha Hampton scored 12 points for the Blue Demons (8-1), who will face No. 7 Tennessee on Sunday in the Maggie Dixon Classic doubleheader at Madison Square Garden.
DePaul got off to a slow start and trailed 18-9 midway through the first half. When the regulars returned to the court, DePaul put together a 28-9 surge to take a 37-27 halftime lead.
“We weren’t ready to play and that just doesn’t happen here,” Blue Demons coach Doug Bruno said. “I don’t want to take anything away from the kids from Edwardsville, they really deserve credit when they come in and play a game like this.
“A lot of (our) people did some isolated good things, but it was not a team effort.”
Courtney Kenner had 16 points for the Cougars (4-4), who have dropped four of five. Michaela Herrod and Raven Berry each had 12.
“We definitely needed to get off to that kind of start because we knew DePaul can score a lot points in a hurry,” Edwardsville coach Amanda Lewis said. “We were very pleased with our start, we just had too many turnovers.”
Edwardsville had 14 first-half turnovers and 25 for the game, which DePaul converted into 27 points.