USC vs Illinois Prediction, Picks & Odds for September 27 — College Football Week 5

Farmer's prediction: There's no saving Illinois against USC's explosive passing offense.

Douglas Farmer - Betting Analyst at Covers
Douglas Farmer • Betting Analyst
Sep 26, 2025 • 10:35 ET • 4 min read

NCAAF

Match starts: 20 hrs
ILL
39 %
USC
61 %
Read Analysis
Jayden Maiava USC Trojans NCAAF
Photo By - Imagn Images. Southern California Trojans quarterback Jayden Maiava (14) throws.

If no team is as good or as bad as its most recent game, then the Illinois Fighting Illini should not be judged too harshly for their face-plant in a 63-10 loss at Indiana last week.

The worry, though, is that what ruined the Illini’s chances a week ago could be further emphasized by the USC Trojans this week.

My USC vs. Illinois predictions entirely trust the Trojans’ passing game, as the Illini look more and more susceptible in an area that used to be a strength.

Get into my college football picks before kickoff comes at 12 ET on Saturday, September 27.

USC vs Illinois prediction

USC vs Illinois best bet: USC -6.5 (-114)

Illinois used to have a stellar secondary. Particularly when Ryan Walters was the defensive coordinator for the first two years of Bret Bielema’s tenure in Champaign, the Illini excelled on the defensive back end.

A combination of time and injuries has now turned that strength into a weakness, one that had Indiana head coach Curt Cignetii eager to take the top off Illinois’s defense. Cignetti had seen Duke come so close to exploiting that defense, finding a 51% success rate on dropbacks despite four turnovers.

Cignetti knew the Blue Devils blew that game more than the Illini won it. And he trusted the Hoosiers not to make the same mistake.

“Put the Duke game on,” Cignetti said after last weekend’s rout. “The difference in that game was Duke turned it over.”

Indiana proceeded to enjoy successes on 64% of its dropbacks, adding 0.77 expected points per dropback, a rate that is close to the logical maximum.

And here comes the bad news for Illinois: USC’s passing offense has both a better success rate and a better EPA per dropback than Indiana’s this season. The success rates are actually rather similar, but it can be argued the Trojans are about three times as explosive as the Hoosiers are through the air.

Good luck with that, Illinois.

Bielema can try to shorten this game. He can lean on veteran quarterback Luke Altmyer. He can take solace knowing some defensive backs will be healthier this week than last. None of that will save the Illini.

USC vs Illinois same-game parlay

Illinois's secondary has a couple returning pieces that were not in the fold a week ago, but that will not be enough as Jayden Maiava more and more looks like a top-five quarterback in the country. He should connect on multiple long touchdown passes.

Adding his rushing yardage prop is simply recognizing that number is too low, as he as cleared it in three of four games this season.

USC vs Illinois 3-leg SGP

  • USC -6.5
  • Jayden Maiava Over 2.5 touchdown passes
  • Jayden Maiava Over 8.5 rushing yards

Our deep-ball SGP: Trojans Expose Illini DBs

As Indiana abused Illinois's pass defense, the Hoosiers did not lean on their tight ends. The Illini weakness right now is in its defensive backs, and exploiting those yields greater results. USC should follow suit, even as it comes at tight end Lake McRee's relative expense.

USC vs Illinois 4-leg SGP

  • USC -6.5
  • Jayden Maiava Over 2.5 touchdown passes
  • Jayden Maiava Over 8.5 rushing yards
  • Lake McRee Under 32.5 receiving yards

USC vs Illinois odds

  • Spread: USC -6.5 | Illinois +6.5
  • Moneyline: USC -245 | Illinois +198
  • Over/Under: Over 60.5 | Under 60.5

USC vs Illinois trend to know

Illinois has gone 0-3 against the spread in its last three Big Ten home openers. Find more college football betting trends for USC vs Illinois.

How to watch USC vs Illinois

Location Memorial Stadium, Champaign, IL
Date Saturday, September 27, 2025
Kickoff 12:00 p.m. ET
TV FOX

USC vs Illinois latest injuries

USC vs Illinois weather

Monitor gametime conditions with our College football weather info.

Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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Douglas Farmer
Betting Analyst

Douglas Farmer spends his days thinking about college football and his nights thinking about the NBA. His betting habits and coverage follow that same pattern. He covered Notre Dame football for various outlets from 2008 to 2024, most notably spending eight seasons as NBC Sports’ beat writer on the Irish. That was also when his gambling focus took off. Knowing there were veteran beat writers with three decades more experience than he had, Douglas found his niche by best recognizing Notre Dame’s standing in each year’s national landscape, a complex tapestry most easily understood and remembered via betting odds.

In 2021, that interest created a freelance opportunity with Covers, a role that eventually led to Douglas joining the company full-time in 2023. In the fall, Douglas will place five or six dozen bets each week, a disproportionate amount via BetRivers because the operator tends to have lines slightly different than the rest of the market. The same can be said of Circa Sports’ futures markets.

While Douglas is an avid NBA fan and covers the league throughout the year, the vast majority of his bets are on college football, because that is the biggest key to sports betting: Know what you do not know.

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