Michigan State vs. #25 USC Prediction & Best Bets: Can the Spartans Slow Down the Trojans?

USC quarterback Jayden Maiava - Michigan State vs. USC Prediction & Best Bets (9/20/2025)

After racking up more 130 points and 1300 yards in two games, USC took a step back last week against Purdue. But when you still put up 33 points and 460 yards, you still had a good week, and the newly-ranked Trojans will look to keep rolling at home against a fellow 3-0 team. Tonight’s Michigan State vs. USC matchup is set for 11:00 p.m. ET, and night owls across the nation can catch the contest on FOX.

After destroying Missouri State (73-13) and Georgia Southern (59-20) to start the season, the Trojans opened Big Ten play last week with a 33-17 win at Purdue. They did not cover the three-touchdown spread, but they were never threatened by the Boilermakers, who did themselves in with three interceptions in USC territory.

Can Michigan State make things interesting vs. USC? They enter Big Ten play still unblemished, following home wins over Western Michigan, Boston College, and Youngstown State. None of those wins are overly noteworthy, but this is the first time since 2021 that the Spartans finished with a perfect non-conference record.

Will the #25 Trojans secure a second straight week in the rankings and improve to 4-0? Read on for our Michigan State vs. USC prediction and best bets, as well as the best value odds from top online sportsbooks such as BetOnline.

Michigan State vs. USC Prediction and Best Bets

Prediction: USC to win

Last week’s game at Purdue is one that last year’s USC team almost certainly would have found a way to lose or almost lose.

That they bent but didn’t break against the Boilermakers and came up with three crucial turnovers, including a pick-six, is a positive sign, especially with the schedule they have after this game: at Illinois, vs. Michigan, at Notre Dame, and at Nebraska.

This week’s game, while a potential challenge, should be much like last week’s. I like what Aidan Chiles has done thus far this season, and the Spartans appear headed in the right direction after three disappointing seasons.

But their best win to date is a two-point, two-overtime win over Boston College, who lost last week at Stanford, who was picked to finish last in the ACC and is comfortably one of the worst teams in the Power 4.

After throwing 11 interceptions last season, Chiles has just one through three games this season, and continuing to keep mistakes at a minimum will be key for Michigan State to have a chance vs. USC.

That is because the margin for error is razor-thin when the Trojans are clicking at such a high level offensively. They are about to encounter tougher defenses starting next week, but it is difficult to see the Spartans providing significant resistance for Jayden Maiava and USC’s explosive O.

I think the Spartans can put some points on the board, especially if they don’t do what Purdue did three times in plus territory last week.

But all signs point to a fourth consecutive dub for USC and a ranked vs. ranked matchup in Champaign next Saturday afternoon.

Michigan State vs. USC Best Bets

1) Jayden Maiava Over 277.5 Passing Yards (-115 at Lucky Rebel)

Through three games, Maiava has completed 68.6% of his passes for 989 yards and six touchdowns (with no interceptions), and he is averaging 14.1 yards per attempt. Against Purdue, he completed only 60.7% of his passes (17 for 28), but he still threw for 282 yards.

Two weeks ago, Boston College’s Dylan Lonergan was 34 for 45 for 390 yards and four scores against the Spartans, and even last week, Youngstown State QB Beau Brungard (24 for 34, 242 yards, 2 TD, INT) had a solid game despite the significant mismatch.

Expect Maiava to put up some big numbers tonight, which makes receiving yards props for Makai Lemon (over 87.5) and Ja’Kobi Lane (over 57.5) worth a look as well.

2) Michigan State/USC First Quarter Over 13 Points (+100 at BetOnline)

With two good quarterbacks on the field in this Michigan State vs. USC matchup, look for some early points. And with no hook involved, you are protected if there are two touchdowns but someone misses an extra point.

3) Aidan Chiles Over 207.5 Passing Yards (-115 at Bovada)

Chiles went over this number just four times in a dozen games last season, but though he has gone over it in each of the last two games after throwing for only 155 yards in the season opener against Western Michigan.

Also, after attempting more than 24 passes in only five games last season, he has thrown 23, 29, and 29 in his first three games this season. And he is completing his passes at a higher clip. Last season, Chiles completed 60% or more of his passes in only half of his games, but he is already halfway to that number in just three games this season.

Sportsbooks may not be accounting for his numbers to date or the prospect of Michigan State playing from behind, which has set up a lower target for him to have to reach.

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