Michigan State vs USC Picks and Predictions for Saturday, September 20, 2025

By: David Anicetti Published 09/14/2025, 08:35 PM ET

Michigan State and USC meet on Saturday at 11:00 p.m. ET at the Los Angeles Memorial Coliseum. Michigan State improved to 3–0 after beating Youngstown State 41–24, while USC also moved to 3–0 with a 33–17 win at Purdue. The game airs on FOX. Make your best bet with our expert college football picks

Michigan State Preview

Quarterback Aidan Chiles has been efficient, hitting 58 of 81 for 656 yards with 6 touchdowns and 1interception. Nick Marsh has 16 catches for 194 yards and 3 TDs, while Omari Kelly has 184 yards receiving. The run game is steady with Makhi Frazier at 206 yards on 43 carries (4.8 per carry) and two touchdowns. The one concern is protection — the Spartans have allowed 8 sacks, which can stall drives.

Defensively, Jordan Hall leads with 27 tackles, and the line has created some noise with QB pressures and 6 total sacks recorded. Michigan State has bent but held in key spots, yet big plays allowed have hurt the Spartans at times. Michigan State can not allow USC to make catches in the open field and extend plays.

USC Preview

Quarterback Jayden Maiava has led an explosive offense: 48 for 70 for 989 yards, 6 TDs, 0 INTs. The run game is just as dangerous, totaling 720 yards on 103 attempts (7.0 per carry) with 12 rushing TDs. Waymond Jordan leads with 286 yards and 3 TDs. Through the air, Makai Lemon leads with 311 yards and 2 TDs, while Ja’Kobi Lane is second with 239 yards and one touchdown.

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On defense, Eric Gentry leads with 21 tackles, while edge rusher Anthony Lucas (2 sacks). The Trojans have produced takeaways in the secondary (six interceptions) and limited mistakes, allowing the offense to have short fields. If USC wins the early downs and forces predictable passing from Michigan State, its running game can take over late.

Michigan State vs USC Prediction

USC will win by double digits. The Trojans’ balance — explosive rushing, solid passing, and a defense that creates havoc both pressuring the passer and intercepting passes -- is a tough match for a Michigan State offense that struggles in pass protection. Final Score Prediction: USC Trojans win and cover ATS 37-17

Best Pick

USC Trojans -14.5

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