Looking at the best college football bets for Week 2 of the NCAA season. This week includes Illinois against Duke.
Week 2 brings an intriguing NCAA slate with a couple of good matchups and potential statement games. Illinois hits the road against ACC foe Duke, USC looks to dominate for the second straight week and Mississippi State welcomes in #12 Arizona State for their first home game of the season. Here are the three best college football bets to target this weekend.
Best College Football Bets For Week 2
Illinois at Duke
Both Illinois and Duke cruised easily in Week 1 against FCS opponents. Illinois beat Western Illinois, 52-3, while Duke knocked off Elon, 45-17. You can’t take too much from those opening games, but this could be one of the best matchups on the college football slate this week.
The Fighting Illini are led by veteran quarterback Luke Altmyer and a trio of running backs. I expect Illinois to control the pace and run the ball effectively against a Duke defense that gave up 160 yards rushing to Elon a week ago. Duke meanwhile, is led by impressive Tulane transfer Darian Mensah, who threw for almost 400 yards in the opener.
Ultimately, Illinois is just the better team. They come in ranked 11th in the country and have high expectations for this year. It is their first road game, so they could get off to a slow start, but expect them to eventually get the running game going and cover the 3.5-point spread.
Best College Football Bets: Illinois -3.5
Georgia Southern at USC
USC cruised in Week 1, piling up 597 total yards of offense in a dominant 73-13 win over Missouri State. Sure, it was Missouri State and their first-ever game as an FBS program, but 73 points is still 73 points. The Trojans were super-efficient and in control from start to finish.
Georgia Southern is coming off a 42-14 road loss at Fresno State. The Eagles couldn’t stop the run, allowing 351 yards rushing and 7.3 yards per carry.
Expect USC to follow a similar script as last week and get out to a big lead early and never look back. I am not saying they will hang 73 again, but they should cover the 28.5-point spread comfortably at home against Georgia Southern.
Best College Football Bets: USC -28.5
Arizona State at Mississippi State
Mississippi State vs Arizona State could be one of the more entertaining games on the Week 2 college football slate. The Bulldogs are coming off a solid road win against Southern Miss, 34-17. Arizona State opened its season with a win over FCS opponent Northern Arizona, 38-19.
Blake Shapen looked sharp in the season opener for Mississippi State, throwing for 270 yards and a touchdown. The Bulldogs also ran for 188 yards as a team, racking up 465 total yards. On the other side, Arizona State’s quarterback Sam Leavitt opened up the 2025 campaign strong as well, throwing for 257 and two touchdowns, while adding 99 yards and a pair of touchdowns on the ground.
Arizona State comes in ranked #12 in the country and riding the momentum of last year’s playoff run. But hitting the road for the first time and Starkville isn’t an easy place to play. I am not sure if Mississippi State can pull off the upset, but I will take them keeping it within 6.5 points.
Best College Football Bets: Mississippi State +6.5
