Despite losing Nate Longshore in the season opener for the remainder of the year, the Bears would get off to their best start since Steve Mariucci coached them in 1996, starting the season 5-0. But the Bears would stumble and lose 4 of their next 5 games, partly due to poor quarterback play and costly turnovers and mental errors. The team would end up in the 2005 Las Vegas Bowl, where they would beat BYU 35-28.
Cal then hosted the #1-ranked USC Trojans, led by head coach Pete Carroll and an offense including Heisman Trophy-winning quarterback Matt Leinart and running back Reggie Bush. The Trojans scored first after Ayoob's first of four interceptions in the game, on a LenDale White rush. Ayoob recovered after the interception, and led the Bears to a field goal to cut their deficit to four at the end of the first quarter. In the second quarter, Leinart rushed for a pair of touchdowns to give the Trojans a 21–3 lead at half-time. After a pair of White rushing touchdowns, the Bears scored again on a Chris Manderino rush that ended scoring in the game, with the Trojans winning 35–10. With the win, the Trojans clinched at least a share of the Pac-10 title.