Corey Stokes and Corey Fisher had 16 points each, and Dominic Cheek contributed 14 for the Wildcats (8-1), who overcame an eight-point deficit in the final five minutes for their ninth straight victory over the Explorers (6-4).
Jerrell Williams scored 20 points to lead four La Salle players in double figures. Sam Mills had 14 points, Tyreek Duren 13 and Ruben Guillandeaux 10.
Duren's two free throws with 5:23 remaining put La Salle up 74-66, matching its biggest lead of the second half, before Villanova went on a 12-2 run to take a 78-76 lead with 3:06 left. Cheek capped the run with consecutive 3-pointers.
Mills answered with a 3-pointer with 1:43 left to give La Salle a 79-78 lead with 1:43 remaining. But Villanova retook the lead on Wayns' crucial three-point play, a driving layup and free throw that put the Wildcats up 81-79 with 1:09 left.
La Salle's Aaric Murray missed an 8-footer that would have tied it on the Explorers' ensuing possession. After Fisher missed a 3, Villanova's Mouphtaou Yarou came down with a big rebound and Fisher made two free throws to give the Wildcats an 83-79 lead with 13.5 seconds left. After Duren made two free throws to pull La Salle within 83-81, Fisher made 1 of 2 from the line with 10.1 seconds left and Villanova led 84-81.
The Explorers had two chances to tie in the final seconds, but Maurice Sutton blocked Mills' 3-point attempt with four seconds left before Mills' final attempt from 33 feet bounced off the rim.
La Salle took its biggest lead of the game at 20-6 with 11:40 left in the first half, as Villanova started the game shooting 1 of 15 from the field, including missing five 3-point attempts. But the Wildcats scored 25 of the next 33 points while making 8 of 9 shots to take their first lead, 31-28, with 4:43 left in the half on Cheek's second straight 3-pointer. Villanova, which committed a season-high 18 turnovers, led 38-37 at halftime.
