Michigan State Spartans vs USC Trojans Prediction, Odds and Picks for Today, 09/20/25

Michigan State hits the road to face USC in the Big Ten opener on Saturday night. The Spartans are unbeaten in three games, but they’re failed to cover in any of the three games to date. The defense has been an issue. After opening with a respectable performance in a 23-6 win over Western Michigan, the Spartans allowed 40 points in an overtime win over Boston College, and 24 points to FCS Youngstown State. That’s a pair of over results in the past two games, with Sparty averaging 41.5 PPG.

USC also enters with three wins in three games. It won the Big Ten opener at Purdue last Saturday, 33-17, failing to cover as a 20.5-point favorite. It was able to have its way in the first two games, going for 73 points against Missouri State, and 59 points against Georgia Southern, but against a Power 4 team, the Trojans saw the offense have a little more of an issue. The defense has been pretty decent for USC, but it has allowed at least 13 points in each game. USC could struggle with QB Aidan Chiles and the Spartans, who have a respectable offense. The spread is quite high, and you can expect Michigan State to grab its first cover of the season.

Michigan State vs USC prediction: Michigan State Spartans +18.5 (-110) at time of publishing. Playable to +17.5.

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