The Notre Dame Fighting Irish take on the USC Trojans. Check out our college football odds series for our Notre Dame USC prediction and pick.

This is what makes college football special. Notre Dame versus USC is the greatest intersectional rivalry in college football. The vast majority of college football rivalries are in-state battles, local feuds which are special because the players involved generally went against each other on the gridiron in high school. Parents and alumni know each other and are part of a tightly-knit cultural and social circle in a city or corridor within a state. Notre Dame versus USC is different. It is a Rose Bowl unto its own, Midwestern sturdiness against California freedom. It is the geographical clash and contrast which is a preview or prequel (take your pick) to the Rose Bowl each January 1.

When Notre Dame and USC are both really good if not great, this rivalry sizzles. These two schools have produced numerous Heisman Trophy winners and have won fistfuls of national championships. In the 1960s and 1970s, there was no better rivalry in college football.

Notre Dame won the national championship in 1966. USC won the national title in 1967.

USC won the national championship in 1972. Notre Dame won it in 1973. USC won it in 1974. The games played every year between the two schools at that point in college football history were the stuff of legend, and are still talked about today.

For most of the past 30 years, Notre Dame and USC have not been great at the same time. In the 1990s, Notre Dame was a powerhouse under coach Lou Holtz, while USC languished. Then, in the early 2000s, USC rose to prominence under Pete Carroll while the Irish strugled to find a foothold.

This year, we have something close to the golden days of the rivalry — not quite the ideal situation, but certainly better than we have had in most of the past two decades. Notre Dame is 8-3 and ranked in the top 20 after beating Syracuse and Clemson and stringing together several consecutive victories. First-year head coach Marcus Freeman has taken his lumps but has not sulked or complained. He has fought through a lot of adversity and has made improvements to the Irish as the year has gone along.

USC is 10-1, headed for the Pac-12 Championship Game in Year 1 of coach Lincoln Riley’s tenure. The Trojans are alive in the College Football Playoff race, but they have to focus on Notre Dame first and can’t get caught up in the national conversation. This is the first Freeman-Riley duel, and it should be special under the lights in Los Angeles. This is the first Notre Dame-USC game in L.A. since 2018, because the 2020 game was canceled due to the pandemic.

Courtesy of FanDuel, here are the Notre Dame-USC College Football odds.

College Football Odds: Notre Dame-USC Odds

Notre Dame Fighting Irish: +5.5 (-110)

USC Trojans: -5.5 (-110)

Over: 64.5 (-104)

Under: 64.5 (-118)

Why Notre Dame Could Cover the Spread

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The Irish can cover the spread because they have an elite special teams unit, a great defense, and a strong offensive line. That last ingredient, the offensive line, can mash the ball between the tackles and grind down the clock, keeping the ball away from USC Heisman candidate Caleb Williams.

Why USC Could Cover the Spread

After all else is said about this game, it comes down to the fact that USC has an elite quarterback, Caleb Williams, and Notre Dame has a very mediocre quarterback, Drew Pyne.

Final Notre Dame-USC Prediction & Pick

Notre Dame’s defense is superb and its special teams are outstanding. However, the quarterback position still matters. Caleb Williams will enable USC to cover the spread.

Final Notre Dame-USC Prediction & Pick: USC -5.5