USC Trojans vs Oregon Ducks Prediction, Odds and Picks for Tomorrow, 11/22/25

One of the most important games in the nation comes in the Big Ten on Saturday, when the USC Trojans visit the Oregon Ducks in a game that effectively functions as an elimination game for both teams in the College Football Playoff picture. Oregon has been cruising for most of the season, but the Ducks have struggled a bit when stepping up in class in a couple of spots. In fact, while they have a couple of impressive wins in conference play — including a massive walk-off win against Iowa on the road a few weeks ago — one could argue that a few of those wins haven’t aged all that well compared to how they were perceived at the time. This Ducks team has a ton of talent on both sides of the ball, but most of it is still fairly young, and I’m still of the belief that next year is when Oregon will stake itself as a true national title contender. It’s also worth considering that Dan Lanning’s team was still pretty banged up a week ago and could be without a couple of key starters on offense this week — most notably freshman wide receiver Dakorien Moore — if those injuries carry over. With that in mind, even though Dante Moore was lights out a week ago and the Ducks will be playing in their final home game of the season, this one still has all the ingredients for a game that might be a bit too close for comfort for the Oregon faithful Autzen Stadium.

It’s no secret that USC has had major issues with going on the road in the Lincoln Riley era, but those problems have predominantly shown themselves when the Trojans have needed to traverse multiple time zones to play an unfamiliar opponent. USC’s problems have also largely come as a favorite, which makes this matchup a much different situation for the Trojans. It all starts on offense for Riley’s group, and he’s fortunate to have arguably the best wide receiver duo in the country in Makai Lemon and Ja’Kobi Lane. Together, this elite duo should see success against an excellent Oregon secondary, seeing as the only time the Ducks have struggled against the pass this season came against Indiana, who had a similarly strong duo of wide receivers on the outside. Not only is the Trojans passing offense one of the best in the nation (5th in passing success rate, 4th in EPA per pass), but USC is still a run-first operation, which bodes well against an Oregon defense that is still a pretty middling unit against the run by Power 4 standards. All things considered, I expect both sides to score in a game that could feel like an old PAC-12 shootout. However, the underdog is my preferred choice in this pivotal West Coast showdown. 

USC vs Oregon prediction: USC +10.5 available at time of publishing. Playable to USC +10

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