The Zips took a double-digit lead in the first half and held off the Trojans to beat a Power Five conference member for the fourth straight season.
Noah Robotham added 14 points for Akron, which opened 2-0 for the fourth time in Coach Keith Dambrot's 11 seasons.
USC (1-2) cut Akron's 17-point lead down to 47-40 on Nikola Jovanovic's basket with 10 minutes left. That's when Antino Jackson hit two straight three-pointers to give the Zips back their comfortable lead.
Jovanovic had 11 points to lead the Trojans, who shot just 28.3% (15 of 53) for the game.
This was Akron's first game since senior Demetrius “Tree” Treadwell was suspended indefinitely by the school Sunday. Treadwell had 10 points and 13 rebounds in Akron's opening win over Maryland-Baltimore County last Friday night.
Akron, the only Mid-American Conference team to win 20 games each of the last nine seasons, beat Power Five conference schools Mississippi State in 2011-12, Penn State the next year and Oregon State.