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The odds of college football seeing just its second back-to-back Heisman Trophy winner have taken a major hit.

Caleb Williams, the winner of the 2022 Heisman Trophy, had his worst game of the season on Saturday against Notre Dame as the USC Trojans were soundly beaten in South Bend, Indiana.

Caleb Williams of the USC Trojans looks on during warm-ups prior to the game against the Arizona Wildcats at United Airlines Field at the Los Angeles Memorial Coliseum on October 7, 2023, in Los Angeles. (Katelyn Mulcahy/Getty Images)

Williams threw for just 199 yards with three interceptions as the Trojans turned the ball over five times in the route.

"I made mistakes that I usually don’t make," Williams said. "Nights like that happen. You have to get through it. You got to keep fighting. You have to be a leader."

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USC still has a lot to play for as they remain undefeated in the Pac-12 with a difficult stretch of games ahead of them. Williams will have plenty of opportunities to show why he should be considered for the most prestigious award in college football, but his performance against Notre Dame will not be easily forgotten.

"It’s going to be a battle," Caesars Sportsbook college football lead Joey Feazel told Fox News Digital when asked about Williams' Heisman chances after the loss to the Irish. "And certainly, if he’s able to be the Caleb that we saw last year and win these clutch games and really show out, then he’s absolutely in the mix."

Feazel also alluded to the difficulty in winning back-to-back Heisman awards due to the bias in voting that comes with it, along with USC's