Illinois vs. Duke Prediction, Odds and Key Players to Watch for College Football Week 2

Sean Treppedi | Sep 3, 2025

Illinois’ balanced offense and stout defense make them the safer side against Duke on Saturday. / Ron Johnson-Imagn Images

Duke and Illinois meet in a Week 2 non-conference matchup that feels like a measuring stick for both programs. 

The Blue Devils cruised late against Elon but showed early defensive vulnerability, while Illinois smothered Western Illinois in a game that was never competitive. 

It’s ACC vs. Big Ten, but it’s also a battle of quarterbacks who each opened the season with precision and poise. 

With Illinois favored slightly on the road, this one could reveal which team has the better formula for climbing into the Top 25 picture.

Illinois vs. Duke Odds, Spread and Total

Odds via FanDuel Sportsbook

Spread

• Illinois -2.5 (-120)
• Duke +2.5 (-102)

Moneyline

• Illinois (-146) 
• Duke (+122)

Total

• Over 50.5 (-110)
• Under 50.5 (-110)

Illinois vs. Duke How to Watch

• Date: Saturday, September 6, 2025 
• Game Time: 12 p.m. ET
• Venue: Wallace Wade Stadium
• How to Watch (TV): ABC, ESPN
• Illinois Record: 1-0
• Duke Record: 1-0

Illinois vs. Duke Player to Watch

Luke Altmyer, Quarterback – Illinois

Altmyer’s steady growth under Bret Bielema has turned him into a reliable anchor of the Illini offense. He opened the season completing 81% of his passes for three touchdowns, showing sharper timing than he flashed in stretches last year. His calm decision-making allows Illinois to lean on a balanced attack, with Altmyer distributing efficiently while the ground game softens defenses.

Against Duke, the test will be different: the Blue Devils bring a faster secondary and an opportunistic edge rusher group that thrives on collapsing the pocket. For Illinois to control this tempo, Altmyer needs to avoid negative plays and keep drives alive on third down. If he continues to deliver the ball cleanly and set up explosive runs with play-action, Illinois’ offense will look like one of the more underrated units in the Big Ten.

Illinois vs. Duke Prediction and Pick

The line sitting at Illinois -2.5 reflects market caution, but the Illini’s balance on both sides of the ball makes them the sharper play. Duke’s 45-17 win over Elon looked good on paper, but conceding over 160 rushing yards to an FCS opponent is a red flag when facing Illinois’ physical run game. The Illini rolled up more than 200 rushing yards in their opener, and that three-headed backfield should dictate pace against a Blue Devils defense that isn’t built to win in the trenches.

Darian Mensah impressed with nearly 400 yards passing in Week 1, yet Illinois’ secondary is a different animal, having allowed only 134 yards through the air last week while returning most of its core. Factor in Illinois’ ability to generate pressure without blitzing, and Mensah won’t find the same clean looks he enjoyed against Elon.

Pick: Illinois -2.5 (-120 at FanDuel)

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Odds refresh periodically and are subject to change.

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