Phil Booth contributed 14 for the Wildcats, who improved to 25-3 overall and 12-3 in the Big East while pulling a half-game of first-place Xavier.
Booth had the cast removed from his injured right hand last Friday and was impressive after missing the previous seven games. Jalen Brunson chipped in with 11 and Omari Spellman had 10 points for Villanova.
It was Villanova's 16th consecutive victory against DePaul. The Wildcats shot 34 of 56 from the floor, a sizzling 60.7 percent.
Max Strus led DePaul (10-17, 3-12) with 21 points while Marin Maric added 12.
DePaul's last win against the Wildcats came more than a decade ago on Jan. 3, 2008.
Villanova came out ultra-aggressive in the second half and ripped off a quick 7-0 run to jump ahead 53-30. The run forced DePaul to take a quick timeout just 1:21 into the half.
After a steal, Spellman responded with a 3-pointer, extending the run to 10-0 and the advantage to 56-30.
The Wildcats connected on their first five shots after the break, leading to a 62-37 cushion.
Brunson pushed the lead to 76-46 with a nifty drive to the basket with 9:58 remaining.
That was a large enough edge for coach Jay Wright to play as many as four freshmen at once down the stretch.
DePaul simply couldn't get to the basket and it attempted just one free throw the entire game, going 0-for-1. The Wildcats finished 15 of 21 at the foul line.
Villanova closed the first half on a 19-8 spurt to take a 46-30 lead into the locker room.
Bridges led all first-half scorers with 15 points. The Wildcats shot the ball extremely well, going 16 of 26 (62 percent) before halftime.
DePaul was just 2 of 11 from beyond the 3-point arc and struggled with 10 costly turnovers in the first half. For the game, the Blue Demons shot 43.3 percent from the floor, 4 of 19 from 3-point range and gave the ball away 20 times.
--Field Level Media
DePaul | Villanova | |
Max Strus 21 | Scoring | Mikal Bridges 27 |
Eli Cain 8 | Assists | Jalen Brunson 7 |
Paul Reed 8 | Rebounds | Omari Spellman 7 |
N/A | Free Throws Made | Mikal Bridges 5 |
Paul Reed 2 | Steals | Mikal Bridges 3 |
Paul Reed 1 | Blocks | Mikal Bridges 1 |