With the loss, La Salle (11-8, 3-2) took a damaging hit to a potential at-large bid to the NCAA tournament.
"That's about as tough a loss as you can have in this game," La Salle coach John Giannini said after the Explorers squandered a 10-point lead with 5 minutes, 15 seconds remaining in regulation. "Both teams played with tremendous effort and passion. But it's an extremely hard one to swallow. I don't think you can have a more painful loss.
"In fact, now our challenge is that it's going to be hard to put it behind us, to be quite honest."
In a thrilling back-and-forth contest, VCU's Rob Brandenberg hit consecutive three-point shots to give the Rams (16-4, 4-1) an 88-82 lead in the second OT. The Explorers never recovered.
La Salle couldn't handle VCU's Treveon Graham, a brawny 6-foot-6, 220-pound guard who wrecked the Explorers defense for 34 points.
"Obviously, Graham was shockingly good," Giannini said.
It was the kind of loss that could leave the Explorers with some restless nights ahead, especially if they dwell on a few plays that could have given them the win.
After Graham tied the score at 73 with 9.2 seconds remaining in regulation, 6-11 Steve Zack had the ball under the basket after taking a pass from Tyreek Duren. Zack, who had 11 points, 11 rebounds, and 4 blocked shots, had the time to gather himself but instead rushed an off-balance shot that went wayward.
"I think Steve thought there was less time than there was," Giannini said. "It's not his fault with all the commotion."
Seconds earlier, Duren, a reliable free-throw shooter, missed the front end of a one-and-one with La Salle holding a 73-71 edge and 17.9 seconds remaining.
The Explorers were in front by 69-59 after trailing most of the game, but the Rams continued to lean on Graham, who scored nine of their final 14 points at the end of regulation play.
Tyrone Garland had 30 points for the Explorers; 25 came after the first half. Duren had 15 points and four assists and was steady against VCU's aggressive trapping defense. He played 49 minutes and had only two turnovers against a team that leads the nation in forced turnovers (20.1 a game).