Jonah Matthews scored 14 points and Elijah Weaver added 13 for the Trojans (6-1), who rebounded after their season-opening five-game winning streak was snapped in a 70-61 loss to Temple on Nov. 22.
"I thought it was great team defense," USC coach Andy Enfield said. "Our guards played tough, especially against their perimeter shooters."
Fairfield (1-5) got 16 points from Landon Taliaferro and 13 from Jesus Cruz.
"We fought," Fairfield coach Jay Young said. "Our offensive execution was terrible. I just didn't like the pace we were playing. We got to a late shot clock way too many times and the numbers reflect what we were doing in the late shot clock."
USC overcome an eight-point deficit with 12 minutes left in the first half to take a 25-22 lead at the break.
"I couldn't understand some of the decisions we made," Enfield said. "We just weren't sharp. We probably should have had six or seven more assists but we couldn't finish."
Weaver opened the second half with a pair of 3's to help USC go up 14 points with 8 minutes remaining.
USC dominated in the paint, outscoring Fairfield 24-6. The Trojans also had a 20-4 advantage in fast-break points.
Fairfield shot just 27% (17 of 63) and USC went 20 for 48 (41.7%).
USC: Started a stretch of playing eight of 10 games away from home, including its first three in conference play. It could be a bonding experience for the Trojans, who started two freshmen and a sophomore.
Fairfield: Coming off a 74-55 loss to then-No. 6 Maryland on Nov. 19 in which the Stags went 12 of 25 (48%) from 3-point range and trailed by just nine midway through the second half. Fairfield made 9 of 26 (34.6%) Thursday.
"We wanted to play inside out, and that enabled us to get a couple open looks," Young said. "We shouldn't be taking that many three's, we just shouldn't. We're not a team that can make that many."
USC will play the winner of Davidson-Marquette in the semifinals Friday.
Fairfield will face the loser of Davidson and Marquette Friday in the consolation round.