The 2021 USC Trojans football team represents the University of Southern California in the 2021 NCAA Division I FBS football season. They play their home games at the Los Angeles Memorial Coliseum and compete as members of the South Division of the Pac-12 Conference. They were led by sixth-year head coach Clay Helton in the first two games; Helton was fired on September 13 following the team's 28–42 loss to Stanford. Associate head coach Donte Williams took over as the team's interim head coach.