The Week 4 college football schedule is when conference play officially kicks off for many teams. The Big Ten features the likes of USC vs. Oregon (-3) and Michigan vs. Iowa (+4.5) to make Week 4 college football picks on, with the SEC offering Texas vs. Tennessee (-3.5), with Colorado vs. Baylor (-10) over in the Big 12. Elsewhere, Notre Dame vs. Purdue is always a hotly contested in-state rivalry as the two Battle for the Shillelagh Trophy in their 90th all-time meeting, with the Irish, who are favored by 27.5 points, having won each of the last eight matchups. Claim the latest Polymarket promo code CBSSPORTS to get a $50 bonus after $10 in trades:
Speaking of in-state matchups, Carolinians will look forward to NC State vs. App State (+14), with the Wolfpack looking to rebound after a shocking last-second defeat to Vanderbilt. Meanwhile, one of the largest Week 4 college football spreads has the Miami Hurricanes favored by 41.5 points over Central Michigan. Before locking in any Week 4 college football picks, be sure to see the latest college football predictions from SportsLine's proven model.
The model simulates every FBS game 10,000 times. It is off to a profitable 22-19 start on all top-rated college football picks at betting sites so far this season, and it has been upgraded for the 2026 season to better factor in the transfer portal. Anybody following its picks on college football betting sites could have seen strong returns.
Now, it has turned its attention to the latest college football odds for Week 4 and locked in picks for every FBS matchup. Head here to see every pick.
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Top college football predictions for Week 4
One of the top Week 4 college football picks the model is recommending for best betting apps: Colorado (+10, 54.5) covers at Baylor in a noon ET kickoff. The Buffs were blown out by Northwestern last week, but Colorado has shown resiliency under Deion Sanders, going 11-5-2 ATS after a loss. That 69% cover rate is 10th-best in FBS since Sanders' first season in 2023 (min. 5 games). Meanwhile, no team in college football handles success worse than Baylor in terms of the spread. The Bears defeated Louisiana Tech last Saturday, but Baylor is 0-6 ATS after a win, dating back to 2025. The Buffs cover in well over 50% of simulations in an A-rated pick.
Another Week 4 prediction: USC (+3, 62.5) covers at home versus Oregon at 7:30 p.m. ET in almost 60% of simulations. QB Jayden Maiava sports an 11-1 home record with USC, and the offense looks unstoppable. USC has scored 35-plus in each of the first four games of a season for just the third time in the storied history of the program. Oregon has struggled in its two games versus FBS teams, defeating Boise State by a touchdown, despite being favored by 25.5 points, and losing to Oklahoma State as 24-point favorites. Maiava is projected to have more yards, more touchdowns and fewer interceptions than his counterpart in Oregon QB Dante Moore. The model has USC covering in an A-rated pick and says the Under connects over 60% of the time. See which other picks the model likes here.
How to make college football picks for Week 4
The model has also made the call on who wins and covers in every Week 4 college football game, including a top 5 team which outright loses in one of the week's biggest games. You can only get every pick for every game at SportsLine.
So what college football picks can you make with confidence, and which top-5 ranked team goes down hard? Check out the latest college football odds below, then visit SportsLine to see which teams win and cover the spread, all from a proven computer model that is on a profitable 22-19 run, and find out.
College football odds for Week 4 notable games
See full Week 4 college football picks, odds, predictions here (odds subject to change)
Thursday, Sep. 24 Liberty at Coastal Carolina (+2.5, 52.5) Friday, Sep. 25 Army at Temple (+3, 48.5) Northwestern at Indiana (-21, 49.5) Clemson at California (-1.5, 50.5) Saturday, Sep. 26 Texas at Tennessee (+4.5, 56.5) Illinois at Ohio State (-27.5, 53.5) Colorado at Baylor (-10, 54.5) Notre Dame at Purdue (+27.5, 57.5) Oklahoma at Georgia (-14, 43.5) Ole Miss at Florida (-3.5, 60.5) Iowa at Michigan (-5.5, 38.5) Texas A&M at LSU (-9.5, 52.5) Oregon at USC (+3, 62.5)
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