USC Trojans vs Notre Dame Fighting Irish Prediction, Odds and Picks for Today, 10/18/25

One of the most consequential games on the college football slate this weekend comes in South Bend, Indiana, where the Notre Dame Fighting Irish will host the USC Trojans in a battle of teams that are looking to stay alive in the College Football Playoff picture as the season passes the halfway point. A week ago, I was all over the Trojans to knock off Michigan in what was a great situational spot for Lincoln Riley and this program. And while the spot certainly favors Notre Dame this weekend, this number is simply too inflated, especially now that we’re seeing the Fighting Irish up to a 10-point favorite at some outlets. There are injury concerns on both sides, but I ultimately have confidence in USC to hang around in a game that should feature plenty of points.

Notre Dame has been rolling of late, but it’s fair to suggest that this week’s matchup will be a massive step-up in class for an Irish defense that while improving a bit, is still 90th in success rate allowed, 94th in quality drive rate allowed and 82nd in Early Downs EPA. From a matchup perspective, I don’t see how Notre Dame will be able to slow down Makai Lemon in the slot, especially since that has been the weakness of its pass defense to this point. Overall, the Irish secondary is 92nd in passing success rate allowed for a reason, and I’m curious to see how they’ll handle Jayden Maiava and the USC passing attack (4th in passing success rate, 3rd in EPA per pass, 5th in Early Downs EPA and 6th in 3rd down success rate). The weather forecast in this game is one that should favor Notre Dame on paper, as rain is expected, particularly in the second half. However, USC has shown that it is perfectly capable of lining up and running the ball against a strong defensive front, as we saw against Michigan a week ago. While I have a lot of respect for how well CJ Carr and the Irish offense are playing, I just can’t get to this number now that we’re seeing a double-digit spread on Saturday.

USC vs Notre Dame prediction: USC +10 available at time of publishing. Playable to USC +9.5

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Regardless of which teams wins and/or covers the spread, the over is the only way I can look in this one. In fact, even with potential weather in the forecast, I’m pretty bullish on both offenses in this matchup. I’ve extolled the virtues of this elite USC offense all season, and the Trojans should see plenty of success against a Notre Dame defense that is not only a struggling unit, but is also banged up on the defensive line and the secondary. Conversely, the USC defense has struggled against the run and on key downs all season long (94th in rushing success rate allowed, 76th in 3rd and 4th down success rate), and that should continue against a dynamic running back room of Jeremiyah Love and Jadarian Price for the Irish at home. If either passing offense gets going early on, we could certainly be in for a shootout in South Bend.

Over 60.5 available at time of publishing. Playable to 61.