Mike Best finished with 10 points for Irvine, which shot 7 of 16 (43.8 percent) from 3-point range and remained tied with UC Santa Barbara and Long Beach State for first place in the Big West Conference.
Cal Poly (8-13, 4-4 Big West Conference) scored on five of its first six possessions and led 15-9 with 14:46 left in the first half. UC Irvine, however, rattled off 20 of the game's next 22 points, opening up a 12-point advantage about 7 minutes later.
The Anteaters (14-9, 5-2) took a 39-28 lead into the break.
UCI opened the second half with an 8-1 spurt, extending its lead to 18, and Cal Poly never threatened again.
Chris Eversly paced the Mustangs with 14 points and 10 rebounds.