Wyatt was 7-of-11 shooting and knocked down 3 of 4 3-pointers. Lee scored 20 points and grabbed 10 rebounds for his third double-double of the season.
The Owls (11-4, 1-1) made 47.9 percent (23 of 48) from the field and connected on 5 of 11 3-point attempts.
Rob Loe led the Billikens (12-4, 1-1) with 17 points on 7-of-11 shooting, including 3 of 4 from 3-point range. He added 11 rebounds for his first career double-double. Dwayne Evans added nine points and 13 rebounds.
Saint Louis threatened late, getting within 58-54 on Mike McCall Jr.'s free throws with 38 seconds left. Wyatt hit two foul shots on the ensuing possession, though, and after a Billiken miss, Lee added two more free throws.
Former Michigan point guard Spike Albrecht will play for Purdue as a graduate transfer next season.
Only six major-conference teams have failed to win an NCAA tournament game since the turn of the century. When will each program snap the streak?
Bruce Weber's Kansas State team earned a share of the Big 12 title three years ago, but a lot has changed since then and the pressure is on.