The Trojans posted a short news release to the athletic department website, saying that athletic director Pat Haden informed Kiffin of the decision "upon the team charter's arrival back in Los Angeles" after the defeat, USC's seventh in 11 games.
USC spokesman Tim Tessalone confirmed the decision when contacted by The Associated Press.
Kiffin went 28-15 at USC in parts of four seasons, but his team is 0-2 in conference play for the first time since 2001. And this stay like many of his other jobs comes with a quick, tumultuous exit.
He was an NFL head coach at age 31, a head coach in the Southeastern Conference at 33 and USC's head coach at 34. If there was a consistent trend to those stops with the Oakland Raiders, Tennessee and the Trojans, it was turmoil.
With Oakland, he lasted only 20 games and his departure became a messy, public feud with Al Davis, the late Raiders owner. His arrival in Tennessee was not warmly received by all Vols fans, given the loyalties many had to the former coach there, Phillip Fulmer.
And then came the USC era.
Kiffin faced enormous expectations at USC, especially last season, when the Trojans started out ranked No. 1 in the country. USC wound up falling out of the top 10 by mid-September, and out of the poll entirely by November ending the season as the first team in nearly a half-century to open No. 1 and finish unranked.
It was an all-out free fall a year ago for USC, which lost five of its last six games.
The Trojans were hit with severe NCAA sanctions a few months after Kiffin arrived. He had nothing to do with the wrongdoing that wound up costing the school 30 scholarships over three years and the right to go to the postseason twice but it set the tone for another bumpy ride.
Between the sanctions and injuries, the Trojans played at Arizona State on Saturday night with 56 recruited scholarship players; teams are allowed 85 scholarships. The lack of depth was evident at times in that game, and in the end, Kiffin was held ultimately responsible.
USC said in the statement announcing Kiffin's firing that Haden will hold a news conference later Sunday. The firing comes less than five months after Haden said that Kiffin had, given the sanctions and other issues, "been as good as he can be."
USC next plays Oct. 10 against Arizona, so the Trojans have a bye week to try to settle the coaching situation and get some players healthy. USC may have lost wide receiver Marqise Lee to a left knee injury. He is expected to have his knee evaluated later Sunday in Los Angeles.
"It didn't look very good," Kiffin said after Saturday's game. "It didn't sound very good or look very good, so that's all I got for you."
Hours later, Lee's health became just one of the huge problems facing USC's proud, storied program.
Kiffin addressed his spot on the proverbial "hot seat" after Saturday's loss, saying he's fine with it and that his own job security is "the last thing I'm worried about."
"We have to find a way to coach better," Kiffin said.
Instead, USC and Haden now have to find a different coach.
"I think the guys on this team really do care and can turn this thing around," USC quarterback Cody Kessler said a few hours before the firing was announced. "It's going to be hard I'm not going to lie but with the character and leadership that we have, we can do it."