USC athletic director Mike Bohn said assistant head coach Donte Williams will take over in the interim.
“Clay is one of the finest human beings I have met in this industry, and he has been a tremendous role model and mentor to our young men,” Bohn said in a statement. “We appreciate his many years of service to our university and wish him nothing but the very best. Consistent with our values as an institution, he deserves the utmost respect from the Trojan Family during this transition.”
Bohn added: “Our university and its leadership are committed to winning national championships and restoring USC football to glory. I accept the enormous responsibility I have to our current and former players and the entire Trojan Family to live up to our incredible heritage.”
USC will launch a national search for a new head coach.
USC started the season with a 30-7 victory over San Jose State but lost Saturday to Stanford, 42-28.
Helton took over in the interim for USC in 2013 and led the team to a Las Vegas Bowl victory. But he was not awarded the head coach job. Lane Kiffin started the season as head coach that year followed by Ed Orgeron.
In 2014, Steve Sarkisian was the head coach but he was let go in the middle of the season to deal with personal issues. Helton was named the interim head coach again and later the full-time head coach.
Helton’s 2016 Sam Darnold-led squad won the Rose Bowl and finished No. 3 in the AP rankings, but that would be the highest–ranking for the team under Helton. The team was 11-3 in 2017 but would never finish with 10 or more wins again.
Williams is in his second season on the USC staff. He was the cornerbacks’ coach for Oregon in 2018 and 2019.