VCU used a 13-0 run to take control in the first half and led Purdue 42-32 at halftime.
The No. 3 seed Boilermakers led 24-23 with about 6:30 minutes left when VCU made its run.
Purdue missed five shots, had a turnover and JaJuan Johnson missed the front end of a one-and-bonus free throw in the stretch.
And the Boilermakers couldn't stop the Rams.
No. 11 seed VCU made three three-pointers in the run -- it made 4 of 10 in the half. The Rams entered the game having attempted 823 three-pointers on the season.
VCU has mixed up its defenses, using full-court pressure, three-quarter trap, zone in the half court and man-to-man.
Purdue had only four turnovers in the half but took several ill-advised shots. Ryne Smith was the only efficient one on offense, making 5 of 7 shots (4 of 6 threes) and scoring 14 points.
Johnson had nine points on 4-of7 shooting and six rebounds. Lewis Jackson has four assists and no turnovers but has made only one of four shots.