Michigan State vs USC Prediction, Pick & Betting Line (Sep. 20)

• Michigan State travels west to Los Angeles to take on USC in Week 4 college football action!
• Right now, the Michigan State vs USC odds favor the Trojans by 19.5 points
• Read below for the Michigan State vs USC prediction, pick and the betting line

This game figures to be pretty routine for USC. Now, the Trojans know what they face after the Spartans. Illinois, Michigan, and Notre Dame are next and two of those three are away from the Rose Bowl.

Lincoln Riley knows he must get his team ready, even for the 3-0 Michigan State team. The game kicks off just after 11:00 pm ET.

Michigan State vs USC Betting Lines

USC is favored by 19.5 points with a -1000 moneyline, implying a 90.91% win probability for the Trojans. Michigan State rolls in as +650 underdogs with a 13.33% chance of upsetting the 25th-ranked USC.

The total is set at 55.5 points, with a tiny bit of juice on the Over at -108.

Odds as of September 20, 2025, at DraftKings Sportsbook. Examine the best College Football betting apps for Michigan State-USC.

Michigan State vs USC Predictions

• Game Winner Prediction: USC
• Prop Prediction: Aidan Chiles 210+ passing yards (-107 ML at DraftKings)

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Now, West Virginia flipped the script last week and played almost a perfect game against Pitt. The Mountaineers managed to rack up 31 points and win. On the bright side, the Under snuck in at the last possible minute (55.5 game total be damned). Anyway, USC has shown early that they can score tons of points and guess what, Michigan State can too. Both have played inferior competition to put it kindly.

For Michigan State, few probably expected them to be 3-0, but here we are. They hung on for dear life against Boston College. Then, the Spartans took care of business against Youngstown State. USC enters the Top 25 on the strength of a 33-17 road win at Purdue. Honestly, it is more the teams that fell above them. Anyway, they have piled up 165 points on the young season. Jayden Maiava has racked up 989 yards and six passing touchdowns.

Jonathan Smith and the Spartans are in a tough spot. Going all the way to California is rough, and then Michigan State plays at Nebraska next Saturday. Both teams may need that game more than they realize. Anyhow, Aidan Chiles is a solid dual-threat quarterback for Michigan State. The USC defense could get tested a bit, even at home.

USC now has +300 odds to make the College Football Playoff. More than likely, this number is not going to last. Every season, the same is said about the USC defense. Just wait a few weeks. There may not be that long of a wait, given their schedule.

USC may win the game, but expect Chiles to have a solid night for Michigan State. He could potentially get closer to 250 yards if USC goes up early. Think “garbage yards”.

Michigan State vs USC Picks:

Now, when spreads move like this, I admittedly worry. The adage won’t get fooled again is balanced by gee, that happened? This contest opened as low as 13.5 and is now at 19.5. Did USC get magically that much better overnight? Is it because they are now ranked?

Sure, injuries play a role but nothing has occurred which is earth shattering. Think of what West Virginia pulled off last Saturday. Anything feels kind of possible after that.

Like we said, no one knows what the result will be IF USC gets tested early this week. Honestly, the Trojans might not either.

The question now is, can they finally live up to the hype? Alright, Nick Saban asked about the defense. So does everyone else. Can USC take care of business then upend Illinois on the road? Those are mighty big questions.

I am going for a closer finish than expected. Michigan State has the talent to at least keep up with USC. Their question is can they carry the momentum on the road?

Saturday CFB Picks:

• Michigan State +19.5 Spread (-112)
• Game Total over 55.5 (-108)

Michigan State vs USC Head-to-Head

The programs have met eight times. Here are how the last four went:

• September 14th, 1990: Michigan State 17, USC 16 – Sun Bowl
• September 16th, 1988: Michigan State 20, USC 17 – Rose Bowl
• September 7th, 1987: Michigan State 27, USC 13
• September 29th, 1978: USC 30 Michigan State 9

Now, this is their first meeting since 1990!

Expect USC to try to outscore its problems on Saturday night. Can Michigan State slow that down?