College football predictions: USC vs. Oregon among best CFB spread picks for Week 13

We've got just two full weeks of the 2025 college football regular season left as teams continue to improve or slip up when it comes to College Football Playoff and conference title game races. With only two weeks left, teams on the bubble can't afford any more lapses. As we do every week, we've highlighted five of our favorite spread bets for the weekend's top college football games, and all five of these matchups have major CFP and conference implications. 

All odds are courtesy of DraftKings Sportsbook, where you can get $200 in bonus bets and three free months of NBA League Pass:

Best college football spread picks for Week 13

No. 16 USC (+10) at No. 6 Oregon

This is it for the Trojans. At 8-2, another loss effectively eliminates them from CFP contention. USC faces a struggling UCLA team next week, so a win this week could very well help the Trojans punch their ticket to the playoff. The issue is they have to head to Eugene for a date with the Ducks. Oregon survived scares against Wisconsin and Iowa before blowing out Minnesota last week. USC presents a different challenge than those three teams with its high-powered offense, and this is the best unit Oregon has faced since allowing 30 points and losing to Indiana at home. I'm not sure if USC can win this outright, especially at Autzen, but the Trojans have to pull out all the stops here, which makes them especially dangerous. Oregon always wants to jump out early and boat race its opponent, but that won't be easy this week against a dangerous USC team that's feeling good after a win over the Hawkeyes.

No. 23 Missouri +7.5 at No. 8 Oklahoma

The Tigers snapped a two-game losing streak with a blowout of Mississippi State last week thanks to a ridiculous 300-yard game from running back Ahmad Hardy. The Tigers would love to run the ball like that every week, but this is a different test against an Oklahoma squad that knocked off Alabama at home. Even after that win, I still have some slight reservations about the Sooners, though they look a lot more legit than they did a week or two ago. Oklahoma should win this, especially as the Tigers have had to turn to a freshman quarterback in Matt Zollers, but the Tigers have been able to keep things close against tough foes outside of the blowout loss to Texas A&M. 

SMU (-3) vs. Louisville

What a weird year for Louisville. The Cardinals were 7-1 with wins over Pittsburgh and Miami at one point, but they've lost back-to-back games to Cal and Clemson, effectively ending their ACC title game hopes. SMU made the CFP last year and also knocked off Miami and at 5-1, the Mustangs are one of four teams in the ACC with just one conference loss. SMU has a lot more to play for here, which can either energize a team or make them fall flat. We'll back the former happening here, especially as the Mustangs have won four straight home games and five of six after a 2-2 start. It looks like we've seen the best of the Cardinals already while SMU is playing its best football at the right time, which is what happened last season.

No. 15 Georgia Tech (-2.5) vs. Pittsburgh

The Yellow Jackets recovered from their loss to NC State with a narrow win at Boston College. They face a Pittsburgh team that is 5-1 in conference play, making this a monumental ACC clash where the winner may very well punch its ticket to the conference title game. Georgia Tech has lost just that one game to NC State while Pitt fell to Louisville in conference play as well as West Virginia in September and to Notre Dame in blowout fashion. While the Yellow Jackets have played more close games than you'd like if you're a fan, they have just the one blemish on their resume. This game is at home, too, where Georgia Tech is undefeated. This should be a close one, but the Yellow Jackets have been the better team all year long and have to win this one, especially with a clash against Georgia on tap next week.

No. 11 BYU (-2.5) at Cincinnati

BYU bounced back from its blowout loss to Texas Tech with a resounding win over TCU over the weekend, and its next test is a Cincinnati squad that's dropped two in a row. The Red Raiders are in the driver's seat for the Big 12 title game as they're 7-1 in conference play. The Cougars are the lone other one-loss team in Big 12 play this year, and they hold a key tiebreaker over Utah. Cincy has two conference losses, so a win this week would tie the Bearcats with BYU but give them the head-to-head tiebreaker. Cincy didn't lose to slouches by any means, but the Bearcats were blown out by a Utah team that BYU beat in October. That doesn't always translate but it does give us a good barometer. It feels like we've seen the best of the Bearcats and it's not quite up to par with the Cougars, especially in Provo.