Leading 44-43 midway through the second half, UC Irvine used a 17-2 run and rolled to its fifth straight win.
Will Davis II scored 14 points and Luke Nelson matched a career-best with eight assists for UC Irvine (12-8, 5-1 Big West), which played its fourth straight game without 7-6 sophomore center Mamadou Ndiaye because of a left foot injury.
Reese Morgan scored 13 of 17 points in the second half, and Cal Poly pulled within 63-55 with less than a minute to go. Davis answered with a dunk, and Souza made a pair of free throws to seal it.
Joel Awich added 13 points and eight rebounds for Cal Poly (10-9, 3-4).