Joel Awich hit a 3-pointer to give Cal Poly (8-10, 4-1 Big West) a 58-53 lead with 3:05 remaining, but it turned out to be the last time the Mustangs scored.
However, Cal Poly limited the Titans (6-12, 1-3) to just a point in the final 3 1/2 minutes to hold on for the win. Alex Harris missed a jumper which would have tied the game with 2 seconds left for Cal State Fullerton.
Cal Poly scored 11 straight points early on, racing to a 17-5 lead. The Mustangs are off to its best Big West start in its program's 18 years as a conference member.
Michael Williams led Cal State-Fullerton with 20 points.