College Football Week 2 Best Bets: Michigan-Oklahoma Grabs Spotlight

By Bill Speros Sep 5th, 2025 2:14 PM EDT

Our Week 2 College Football Best Bets feature one Top 25 matchup and a handful of old-time out-of-conference rivalries. The full Power 5 intra-conference schedules begin next week for you to bet on at the best sports betting apps.

Michigan and Oklahoma grab the national TV spotlight on Saturday night. Both teams look to score an impressive out-of-conference win that could help with seeding come playoff time. The Sooners have yet to find traction in the SEC. But they scored a preseason No. 18 ranking. OU overhauled its offense with a new QB (John Matier), new lead running back (Jayden Ott) and a new offensive coordinator (Ben Arbuckle).

The Wolverines came off a national championship season last year and were the final team to beat Ohio State before the Bucks rebounded and won the Natty in January.

Michigan swiped QB Bryce Underwood from LSU, hired a new OC in Chip Lindsey, and brought in WRs Donaven McCulley (Indiana) and RB Justice Haynes (Alabama) from the portal.

Other Week 2 College Football Best Bets include:

The annual Iowa-Iowa State clash – this time in Ames
Baylor facing home-state Texas rival SMU
An SEC matchup between Ole Miss and Kentucky

Week 2 College Football Best Bets

Here are our Week 2 College Football Best Bets to back on your favorite sports betting sites.

Date	Matchup	Week 2 Best Bets
Sat. Sept. 6	Illinois at Duke	Illinois -2.5 (-100) DraftKings
Sat. Sept. 6	Baylor at SMU	SMU -3.5 (-110) DraftKings
Sat. Sept. 6	Iowa at Iowa State	Iowa +3.5 (-115) DraftKings
Sat. Sept. 6	Ole Miss at Kentucky	Kentucky +9.5 (-110) DraftKings
Sat. Sept. 6	Kansas at Missouri	Kansas +6.5 (-102) FanDuel
Sat. Sept. 6	Oklahoma State at Oregon	Oregon -23.5 (-110) DraftKings
Sat. Sept. 6	Arizona State at Mississippi State	Mississippi State +10 (-110) DraftKings

The locals are always ready for the Cyclones and Hawkeyes. (USA TODAY)

Week 2 College Football Best Bets: Game-By-Game Analysis

Saturday, September 6

Iowa at Iowa State, 12 p.m. (FOX)

Buzz: One of college football’s most intense rivalries resumes in Ames. Two evenly matched teams make this game perhaps the weekend’s most compelling watch. But don’t expect much offense. Last year, Iowa State scored 20 points in the 2^nd half to wipe out a 13-0 lead and win 20-19 on a last-second kick. Expect a similar outcome this time.

Best Bet: Iowa +3.5 (-110) at DraftKings via OddsJam

Illinois at Duke, 12 p.m. (ACC/ESPN)

Buzz: The No. 12-preseaon Illini need a decisive win against ACC foe Duke to maintain their top 20 spot. Illinois defense is the difference here. Along with an offensive line that will stifle the Devils.

Best Bet: Illinois -2.5 (-110) at DraftKings via OddsJam

Baylor at SMU, 12 p.m. (CW)

Buzz: The Mustangs earned a top-20 preseason ranking after a solid first year in the ACC. Kevin Jennings returns at QB, but SMU lost Brashard Smith at the running back position. The SMU offensive line will be tested here. Baylor may still be gassed after its season-opener at home against Auburn.

Best Bet: SMU -3.5 (-110) at DraftKings via OddsJam

Ole Miss at Kentucky, 3:30 p.m. (FOX)

Buzz: The Wildcats went 4-8 last year and bring 50 new players to their SEC opener at Kroger Field. But they know Lane Kiffin well. Kentucky derailed the Lane Train on its way to the SEC title game with a 20-17 upset in Oxford last season. This time, Ole Miss QB Austin Simmons makes his first road start. Large SEC point spreads often go to Kroger Field to die.

Best Bet: Kentucky +9.5 (-110) at DraftKings via OddsJam

Kansas at Missouri, 3:30 p.m. (ESPN2)

Buzz: Both Missouri and Kansas can be considered up-and-coming entities in their conference. The Tigers went 10-3 last season but failed to break through the iron of the SEC. Kansas was in the Big 12 chase – along with about 10 other teams – into the final 2 weeks of the season. Kansas dominated Fresno State, winning 31-7 off a 13.5-point line. Mizzou tunes up against Central Arkansas this week. The price on KU is too good to pass here for our Week 2 College FootballBest Bets.

Best Bet: Kansas +6.5 (-102) at FanDuel via OddsJam

Oklahoma State at Oregon, 3:30 p.m. (CBS)

Buzz: The Pokes may wish they died of dysentery on the Oregon Trail. The Ducks need style points come playoff time if they miss out on the Big Ten title game. Don’t expect any sort of a let-up in the 2^nd half.

Best Bet: Oregon -23.5 (-110) at DraftKings via OddsJam

Delaware at Colorado, 3:30 p.m. (FOX)

Buzz: Coach Prime came one "Hail Mary" short against Georgia Tech. But the Buffs showed plenty of promise in the post-Sheduer Sanders/Travis Hunter era. Delaware visits Boulder for a nice payday. They'll earn it in terms of a long day on the road.

Best Bet: Colorado -23.5 (-110) at BetMGM via OddsJam

West Virginia at Ohio, 4 p.m. (ESPNU)

Buzz: Oddsmakers call for a close matchup between Big 12 entry West Virginia and MAC contender Ohio. The Mountaineers are a 3.5-point road favorite. The Bobcats would love nothing more than to knock off a Power 4 foe at home, where they went unbeaten last season. Ohio fell short against Big Ten foe Rutgers last weekend, losing 34-31. Look for the 'Cats to claw their way to a cover.

Best Bet: Ohio +3.5 (-118) at FanDuel via OddsJam

South Florida at Florida, 4:15 p.m. (SEC NETWORK)

Buzz: All the Power 4 teams based in Florida won in Week 1. This may be the undercard to the Sunshine State Championship given the Florida State-Miami game on October 4. South Florida opened Week 1 with a nifty rout of Boise State in the hot and humid climes of Raymond James Stadium. This week, they're playing in a place called "The Swamp." The Gators tuned up against Long Island. Billy Napier needs to contend in the SEC this year or he'll be calling plays for Kirby Smart next season. The Gators stake their claim starting here.

Best Bet: Florida -17 (-115) at Caesars Sportsbook via OddsJam

Georgia Southern at USC, 7:30 p.m. (FS1)

Buzz: The Trojans hung 73 points on Missouri State Saturday. Don't expect USC to let up here, either.

Best Bet: USC -27.5 (-110) at HardRock via OddsJam

Arizona State at Mississippi State, 7:30 p.m. (ESPN2)

Buzz: Another intriguing Big 12-SEC matchup. The Sun Devils travel to Starkville and get a taste of SEC Saturday night. ASU carries a double-digit number as the road favorite. Oddsmakers (and others) see the Devils as the slight favorite to win the Big 12, barely edging out K-State. The Bulldogs are slotted for also-ran status in the SEC. ASU carried the best record ATS of any FBS team last season at 12-2. Oddsmakers won’t be caught short this time as this number is larger than any price they carried last season. Take the home ’Dogs and the points.

Best Bet: Mississippi State +10 (-110) at DraftKings via OddsJam