The Illinois Fighting Illini take on the Duke Blue Devils at Wallace Wade Stadium in Durham, North Carolina, on Saturday of College Football Week 2. Kickoff is set for 12:00 p.m. EDT on ESPN.
No. 12 Illinois is favored by 2.5 points on the spread with a moneyline of -140. The total is set at 49 points.
Here’s my Illinois vs. Duke prediction and college football picks for Saturday, September 6, 2025.
Illinois Fighting Illini vs Duke Blue Devils Prediction, Picks
- Illinois vs. Duke Pick: Illinois -3 (-110, BetMGM)
My Duke vs. Illinois best bet is on Illinois to cover the spread. Find the best line available on our live NCAAF odds page.
Illinois vs Duke Odds, Spread, Line
| Illinois Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
-2.5 -110 | 49.5 -110o / -110u | -140 |
| Duke Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
+2.5 -110 | 49.5 -110o / -110u | +115 |
Illinois vs Duke Saturday CFB Preview
Illinois Fighting Illini
When you look at the Fighting Illini, the one thing that sticks out about this team is the continuity on both sides of the ball.
Quarterback Luke Altmyer returns for his third season with offensive coordinator Barry Lunney.
In front of him, all five of last year's offensive line starters return and are primed to improve from last season.
They'll be up against a Duke defense that is revamped under former Miami head coach Manny Diaz.
While the Blue Devils have the coaching pedigree leading them defensively, they did not look great against the run in Week 1.
Now the talent ramps up with an Illinois backfield that features a talented committee that should open up the downfield passing game.
Illinois presents several concerns for a Duke defense that is still getting its feet wet in multiple areas. We should see Illinois test the Blue Devils early and often.
Duke Blue Devils
The spread for this matchup is unusually tight, considering Illinois comes in as the No. 11 team in the country and Duke is unranked.
However, it serves as a testament to the Blue Devils' offensive upside.
Quarterback Darian Mensah is a dangerous dual-threat who showed off his passing prowess in Week 1 as he torched Elon for 389 yards and three touchdowns. It appears that the Blue Devils are going to live and die with Mensah this season, as they were pass-heavy, despite leading for the majority of the game against an inferior opponent last week.
Much like the other side of the ball, the Blue Devils will face an Illinois unit that returned nine starters from last year's squad and compiled depth with starting experience through the transfer portal.
So, while Mensah and company may be explosive, the veteran Illinois defense is far from what he faced last week.
Illinois vs Duke College Football Week 1 Pick
While the spread may make these teams appear close, a wide gap in experience exists, and that should play heavily in the Fighting Illini's favor.
We've seen support for Illinois in the market as the week has gone along, pushing this number to three.
A spread pushing through a key number shows that Illinois is the side here, and that should be apparent early in this matchup.
Back the Fighting Illini to cover the spread.
Pick: Illinois -3
