If a team is never as good or as bad as it looked in its last game, then Illinois shouldn’t be judged too harshly for last week’s 63-10 blowout loss at Indiana.
The concern, however, is that the same issues that doomed the Illini in that game could be even more exposed against USC.
My USC vs. Illinois predictions lean heavily on the Trojans’ passing attack, especially as Illinois continues to struggle in a defensive area that was once considered 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.
This is probably the last week I can cite back to Duke's loss to Illinois as reason to doubt Illinois, but if Curt Cignetti could do it, I can do it this last time as reason to bet USC on Saturday, right?
— Douglas Farmer (@D_Farmer) September 25, 2025
Trojans up to -7 and probably by more than that. https://t.co/xM1rWaVOrw pic.twitter.com/sK25SvAwtP
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 game predictions
USC vs Illinois moneyline prediction
Let’s ponder a reasonable game state that would make an upset seem likely. Illinois’s defense has not fared well enough where it matters most to genuinely suggest USC could repeatedly stub its toe in scoring territory. And Jayden Maiava has not thrown an interception yet this season on 96 attempts.
The two most likely ways to spring an upset are thus as unlikely as ever.
There is no such thing as a sure thing, but in this exact matchup, the Trojans look close to it.
USC vs Illinois spread prediction
If Illinois can shorten this game, then perhaps it can stem USC’s passing attack. The hurdle in that regard is that the Illini are no better than okay when running the ball, ranking No. 37 in rushing success rate and No. 40 in EPA per rush attempt, per cfb-graphs.com.
Worse yet, USC has held opponents to distinctly limited rushing success.
USC vs Illinois Over/Under prediction
Though this total has ticked up to 60.5 from its opener of 59.5, one must trust Lincoln Riley does not have the same vindictive tilt that Cignetti does in running up the score on opponents. He does not need to.
Cignetti knows Indiana’s best path into the College Football Playoff is repeated routs. USC just needs to be USC. And Cignetti knows Indiana is recruiting many of the same players that Illinois is. USC is chasing a higher tier of players.
So if Riley is not going to run up the score, trust in any Over is trust in Illinois to find some productivity, and that seems foolish.
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
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