Senior forward Aaric Murray had a monster game for Texas Southern (19-15), scoring 38 points. He made 14 of 23 shots from the floor, including three of five 3-pointers, and he went 7-for-7 from the foul line.
Cal Poly, which finished seventh in the Big West Conference before winning the league tournament, played confidently on Tuesday's big stage.
The Mustangs led by 12 points at halftime and played well in all facets, sans defending Murray, who was the best player on the court throughout the night.
Texas Southern's 10th turnover resulted in senior guard Jamal Johnson's layup that gave the Mustangs a 48-32 lead with 18 minutes left.
The Tigers switched things up on defense, forcing five quick Cal Poly turnovers and cut the deficit to nine.
A three-point play by Texas Southern junior guard Jose Rodriguez made the score 59-51. Rodriguez finished with 14 points.
Early on, Cal Poly had difficulty containing the 6-foot-10 Murray, who began the game with three dunks, including a thunderous one-handed jam in transition. He scored 17 points in the first half.
However, the Mustangs hardly were intimidated.
Freshman guard Ridge Shipley buried a 3-pointer just ahead of the shot-clock buzzer to put Cal Poly ahead 25-19. Despite Texas Southern's size advantage, the Mustangs managed to outscore them 20-16 in the paint in the first half.
Cal Poly was a model of efficiency in the first half with one turnover and 10 assists.