Michigan State vs. USC Prediction, Odds and Key Players to Watch for College Football Week 4

Oddsmakers expect the Trojans to walk right by the Spartans this weekend.

Jayden Maiava and USC are big-time favorites against Michigan State on Saturday. / Marc Lebryk-Imagn Images

The Big Ten is still chock full of undefeated teams early in the 2025 college football season and two of them will face off at Los Angeles Memorial Coliseum this weekend. Michigan State will visit USC on Saturday for an in-conference clash.

The Spartans are 3-0 and will take on a 3-0 Trojans team that’s already secured a conference win against Purdue. The home team is a big-time favorite and is expected to handle the visitors with ease to remain toward the top of the Big Ten standings after the matchup.

Here’s our full betting breakdown of the game ahead of kickoff.

Michigan State vs. USC Odds, Spread and Total

Spread

• Michigan State:+18.5 (-115)
• USC: -18.5 (-105)

Moneyline

• Michigan State: +600
• USC: -900

Total: 56.5 (Over -105/Under -115)

Odds courtesy of DraftKings Sportsbook

Michigan State vs. USC How to Watch

• Date: Saturday, September 20
• Game Time: 11:00 PM EST
• Venue: Los Angeles Memorial Coliseum
• How to Watch (TV): FOX
• Michigan State  Record: 3-0
• USC Record: 3-0

Michigan State vs. USC Key Players to Watch

Michigan State

Aidan Chiles: Chiles threw 13 touchdowns passes and 11 interceptions last season and is looking to make some major improvements in his second season with Michigan State. The third-year quarterback He’s thrown for 656 yards and six touchdowns with just one pick through three games this year and has also run for a score. Chiles might need to get innovative against USC with Makhi Frazier and Nick Marsh banged up.

USC

Jayden Maiava: Maiava surprisingly didn’t throw a single touchdown pass against the Boilermakers after notching six through his first two outings in 2025. He still has the FBS’s fifth-highest passing yardage total (989) and will look to get back on track against a Michigan State defense that’s already been tested by less talented offenses this season. The Trojans have one of the nation’s most dynamic offenses and Maiava’s arm will play a big part in helping them bounce back from a less productive Week 3.

Michigan State vs. USC Prediction and Pick

Michigan State’s outlook isn’t great right now. Its starting running back and leading receiver are both questionable for Saturday and could be limited in practice all week before news regarding their availability for Saturday is made public. The Spartans can’t afford to have a weakened offense against one of the nation’s most potent scoring teams. Especially given how vulnerable their defense has looked.

Michigan State gave up 40 points to Boston College in Week 2 before allowing Youngstown State to score 24 points in Week 3. Bettors should remember that the Trojans were averaging 66.0 points per game before posting 33 points on the road against the Boilermakers in Week 3. Now USC will return to the venue where it’s averaging 676 yards of offense per game.

The Spartans will be at a major disadvantage if any of their key skill players are less than 100 percent and home-field advantage will boost the Trojans’ ability on both sides of the ball. USC has covered the spread in six of its previous seven home games and can keep that strong run going in Week 3.

PICK: USC -18.5 (-105 at DraftKings Sportsbook)

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Game odds refresh periodically and are subject to change.

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