USC vs. Notre Dame prediction: Who wins, and why?

The Greatest Intersectional Rivalry in College Football kicks off under the watchful eyes of Touchdown Jesus, as No. 13 Notre Dame plays host to No. 20 USC on Saturday, and maybe for the last time if somebody doesn’t get their act together.

USC and Notre Dame don’t have an agreement to play this rivalry game after Saturday’s meeting, although both schools have indicated publicly that they want to play it.

Notre Dame wants to because it can likely help boost their College Football Playoff resume every year, but the apparent concern at USC is that this game may not be worth the risk given the perceived quality of its Big Ten schedule in the eyes of the playoff selectors, and some reported travel concerns.

USC is coming off one of the best wins in Lincoln Riley’s tenure as head coach, pulling off an upset against then-ranked Michigan while showing off an improved defense and a legit scoring threat with quarterback Jayden Maiava at the helm, dealing to one of college football’s most productive wide receiver pairings.

Notre Dame started the season 0-2 with both losses against ranked teams, but got the train back on the tracks with four-straight wins, albeit against lesser-quality opponents, and now head into another important matchup against a higher-caliber, ranked team.

USC vs. Notre Dame prediction: What to watch

USC vs. Notre Dame football game prediction 2025 — Michael Caterina-Imagn Images

1. Matchups on Offense

USC fields one of the elite offenses in the country, ranking second nationally in total offense per game (552.3 yards) and first in yards per play (8.3), featuring quarterback Jayden Maiava’s high-efficiency RPO attack and star receiver Makai Lemon.

Notre Dame, on the other hand, has demonstrated strong scoring efficiency at home, averaging a winning margin of nearly 30 points per game recently, but relies on a redshirt freshman quarterback, CJ Carr, who is still gaining experience against top defenses.

2. Strengths and Weaknesses on Defense

Defensively, Notre Dame has struggled up front, ranking outside the top 80 in EPA/rush allowed, which gives USC’s ground game an opportunity to exploit the Irish defensive line.

Both defenses are considered average relative to their offensive outputs, with Notre Dame’s secondary more tested but still liable to yield big plays to USC’s up-tempo passing attack.

3. Red zone execution

USC leads the nation in offensive success rate and efficiency per play, but their red zone touchdown conversion, especially on the road, drops significantly (about 55 percent).

Notre Dame's defense is built to force long drives and tough red zone stands, requiring USC to be precise and efficient to score touchdowns, not just field goals.

Who is favored?

The betting markets are siding very strongly with the Fighting Irish over the Trojans at home, and that interest pushed them into double digits on the books heading into the matchup.

Notre Dame is a 10.5 point favorite against USC, according to the updated game lines posted to FanDuel Sportsbook entering the weekend.

FanDuel lists the total at 60.5 points for the matchup.

And it set the moneyline odds for Notre Dame at -370 and for USC at +295 to win outright.

USC vs. Notre Dame prediction: Who wins?

Notre Dame vs. USC football game prediction 2025 — Gary A. Vasquez-Imagn Images

After a very sluggish start to the season, the Notre Dame defense has been thriving during the four-game win streak, forcing 11 takeaways over that time, tied for the most among FBS teams, and now goes against a USC offense that is tops in college football with over 8 yards per play on average and the nation’s second-ranked aerial attack.

Southern Cal will have to rely more on Maiava to create downfield with Lemon and Lane going deep given the absence of lead backs Waymond Jordan and Eli Sanders while setting its 29th ranked run stop against an Irish backfield that is top 20 with 17 touchdowns and posting nearly 5 yards per carry.

College Football Playoff implications abound in this matchup. Notre Dame needs it more given it has two losses against ranked opponents, and a third would diminish its standing among the selectors later on, potentially to the point of not being considered.

USC is coming off a massive win against then-ranked Michigan and a second-straight victory against a ranked opponent would be a massive boost in the budding postseason picture.

Despite the issues at running back, the Trojans have more than enough firepower to keep this a narrow margin against a Notre Dame defense that has struggled against quality passing attacks.

College Football HQ picks...

Notre Dame wins 34-27
Doesn’t cover the spread
And hits the under

More: USC vs. Notre Dame score prediction by expert model

How to watch USC vs. Notre Dame

When: Sat., Oct. 18
Where: Notre Dame

Time: 7:30 p.m. Eastern
TV: NBC network