Cal Poly (14-19), known more for its shutdown defense than its offensive efficiency, shot a torrid 57 percent from the field in the First Four meeting between the No. 16 seeds.
Chris Eversley scored 19 points, Dave Nwaba netted 17 and Brian Bennett added 10 for the Mustangs, who surprisingly ran through the Big West Conference Tournament as a No. 7 seed and will head to St. Louis to face the Midwest Region's top seed, the undefeated Wichita State Shockers, on Friday.
Aaric Murray did all he could to keep the Tigers' season going, but his 38 point-effort on 14-of-23 shooting went for naught.
Texas Southern (19-15) allowed 23 points off 13 turnovers.