Last year, for the first time since World War II, college football fans did not get to see Notre Dame face USC. But the longstanding rivalry is back this week, as the No. 13 Fighting Irish host the Trojans on Saturday at 7:30 p.m. ET.

Notre Dame is a 6.5-point favorite, as shown in the college football odds table below, marking the first game since November 2020 that USC has been an underdog.

Both teams should be fresh coming off their bye weeks, with as much preparation as possible dedicated to the 91st edition of this rivalry. Find our college football picks for this matchup below.

Odds are current as of publication. betting sites may indicate odds changes closer to kickoff.

5 Keys to USC vs Notre Dame

ND’s QB carousel: Jack Coan began the season as Notre Dame’s starting quarterback, but that job has begun to slip from him. In their last game, the Fighting Irish game freshman Tyler Buchner more attempts (14) than Coan (12). Buchner also carried 12 times and scored a rushing touchdown. Notre Dame coach Brian Kelly said this week that Coan “gives us the best chance to win,” qualifying that statement with “a mixture of him with Tyler Buchner, both of them.”

Will Dart be ready?: USC has a quarterback conundrum of its own, as freshman Jaxson Dart works back from a knee injury sustained in Week 3. Dart entered the game in place of injured starter Kedon Slovis and threw for 391 yards, a USC freshman record. Slovis is still the starter, but Dart returned to practice last week and is on track to return soon. Keep an eye on end-of-week practice reports.

Rivalry renewed: The Fighting Irish’s all-ACC schedule last year interrupted this rivalry, but prior to that Notre Dame had won three in a row (including a 30-27 win in 2019). USC has covered the spread in three of the past four, though, including two consecutive as the underdog.

Mayer makes his return: Notre Dame sorely missed tight end Michael Mayer in its heart-pumping 32-29 victory over Virginia Tech two weeks ago, but Mayer “looks to be 100%” coming out of the bye week, according to Kelly. Despite last game’s absence, Mayer still leads the team in catches (32) and receiving yards (360).

Road warriors: USC has won both its road games handily this season, and it is 4-0 straight up and against the spread on the road dating back to last year. A road date with Notre Dame should look a bit different than facing Colorado or Washington State, though.

USC vs. Notre Dame Weather Forecast

South Bend, Indiana figures to be cool and mostly clear, with mid-40s temperatures and a 20% chance of rain.

USC vs Notre Dame Moneyline

As stated up top, sportsbooks see the Trojans as underdogs for the first time in about 11 months. But given that they’ve lost straight up to unranked teams in two of their past three games, it makes sense. Notre Dame is the justified moneyline favorite (-265) here, and we like them to handle USC at home. Take the Irish at BetMGM.

Up to $1,500 in Bonus Bets if Your First Bet Loses Promo Code: BOOKIES

Tap for Promo Activated! Visit site

Used 45 Times Today

Bonus Bets Expire in 7 Days. One New Customer Offer Only. Must be 21+ to participate & present in OH. In partnership with MGM Northfield Park. Gambling problem? Call 1-800-GAMBLER. Visit BetMGM.com for T&Cs. US promotional offers not available in NY, NV, or Puerto Rico.

USC vs Notre Dame Point Spread

Believe it or not, the Fighting Irish have been underdogs in three consecutive matchups (at Wisconsin, vs. Cincinnati, at Virginia Tech). Betting apps have Notre Dame as 6.5-point favorites in this game, and we believe that’s well within reach.

The Fighting Irish are battle-tested now, and they’ve got their best offensive weapon (Mayer) back in the fold. We’re giving the points at Caesars.

$1,000 First Bet on Caesars

Tap for Promo Activated! Visit site

Used 62 Times Today

OH only. 21+. New users and first wager only. Must register with eligible promo code. Bet amount of qualifying wager returned only if wager is settled as a loss. Maximum bet credit $1,000; must be used within 14 days of receipt. See Caesars.com/promos for full terms. Void where prohibited. Know When To Stop Before You Start.® Gambling problem? Call 1-800-GAMBLER

USC vs Notre Dame Totals

At the start of the college football betting week, this game’s point total shifted slightly down to 57.5. Keep an eye out for additional movement, especially if it dips more.

The Over has hit in four of six games this season for both teams, and we think it’ll happen again – especially if Dart returns on the USC side, and Mayer continues to be an offensive mismatch for Notre Dame. Take the Over at DraftKings.

Bet $5, Get $200 In Bonus Bets Instantly!

Tap for Promo Activated! Visit site

Used 61 Times Today

Must be 21+ and present in OH. Gambling Problem? Call 1-800-GAMBLER.