The win earned the second-seeded Mustangs their first trip to the NCAA tournament.
Griffin tore knee ligaments early in the second half, but Cal Poly was able to maintain the 11-point lead it built in the first half. Griffin had four points in her 24 minutes.
"We wouldn't be in this position without Kayla, there's no question," Cal Poly Coach Faith Mimnaugh said. "I hated that she couldn't be on the court at the end of the game."
Cal Poly (21-10) was the lower-seeded team despite defeating Pacific (25-7) twice during the regular season.
Ariana Elegado led Cal Poly with 22 points, and center Molly Schlemer dominated the boards with 16 rebounds.
Cal Poly held Pacific to 32.8% shooting as the Tigers made only 20 of 61 attempts.
"I don't know, sometimes you have those nights," Pacific Coach Lynne Roberts said of her team's poor shooting.
Gena Johnson led Pacific with 14 points, and Erica McKenzie scored 11.
Pacific, which was 41st in the RPI before the game, is hoping to get an at-large NCAA berth.
"Everything I've heard is that we have a great shot," Roberts said.