College Football Week 4 Opening Lines, Odds & Best Bets: Rebels Hungover in Gainesville

We’re almost a month through the college football regular season at this point, but it feels like the action is just heating up. After an energetic Week 3, the action continues this weekend with another loaded slate, headlined by XX XX

We had a disappointing result last week and are now 2-2 on the year, but it’s a new week with a fresh slate of games. Like every week, let’s highlight the early-week lines and odds for Week 4’s biggest matchups before we cap it off with a best bet. As always, you can find our CFB best bets for our top picks every week, as well as our CFB predictions for tips and analysis on every FBS game this year. 

2026 College Football Week 4 Opening Lines and Odds

Odds courtesy of bet365 at the time of publishing. 

Thursday, September 24

• Liberty -2.5 (-110) @ Coastal Carolina; Total 52.5 (Under -115)

Friday, September 25

• Army -3.5 (+100) @ Temple; Total 48.5 (-110)
• Navy -6.5 (-120) @ UAB; Total 51.5 (-110)
• Indiana -21.5 (-110) vs Northwestern; Total 49.5 (-110)
• California -1.5 (+100) vs Clemson; Total 50.5 (-110)

Saturday, September 26

• Baylor -9.5 (-115) vs Colorado; Total 55.5 (Under -115)
• UTSA -12.5 (-115) vs Colorado State; Total 58.5 (-110)
• Ohio State -27.5 (-110) vs Illinois; Total 53.5 (-110)
• Toledo -2.5 (-120) vs San Diego State; Total 50.5 (-110)
• Texas -5.5 (-110) @ Tennessee; Total 55.5 (-110)
• UNLV -13.5 (-110) @ Akron; Total 50.5 (-110)
• Virginia Tech -14.5 (+100) @ Boston College; Total 50.5 (Over -115)
• Louisville -13.5 (-105) vs Wake Forest; Total 58.5 (-110)
• UCLA -2.5 (-105) @ Maryland; Total 57.5 (-110)
• Notre Dame -27.5 (-115) @ Purdue; Total 57.5 (Under -115)
• Hawaii -3.5 (-105) @ Wyoming; Total 45.5 (-110)
• Boise State -7.5 (-110) @ Western Michigan; Total 48.5 (Under -115)
• Miami (OH) -3.5 (-120) vs UConn; Total 51.5 (Under -115)
• Michigan -5.5 (-110) vs Iowa; Total 38.5 (-110)
• New Mexico -13.5 (-105) @ New Mexico State; Total 48.5 (-110)
• Georgia -14.5 (+100) vs Oklahoma; Total 43.5 (-110)
• Florida -3.5 (-105) vs Ole Miss; Total 60.5 (-110)
• Utah -8.5 (-115) @ Iowa State; Total 49.5 (Under -115)
• Auburn -9.5 (-110) vs Vanderbilt; Total 56.5 (Under -115)
• Nebraska -5.5 (-110) @ Michigan State; Total 48.5 (-110)
• South Florida -17.5 (-110) @ Bowling Green; Total 49.5 (-110)
• Penn State -9.5 (-115) vs Wisconsin; Total 45.5 (Under -115)
• James Madison -5.5 (-110) @ Old Dominion; Total Over 47.5 (-115)
• Kansas State -6.5 (-110) @ Cincinnati; Total 55.5 (-110)
• Arkansas State -5.5 (-110) vs Kennesaw State; Total 53.5 (Under -115)
• West Virginia -1.5 (-115) vs Oklahoma State; Total 60.5 (-110)
• Alabama -12.5 (-110) vs South Carolina; Total 54.5 (Over -115)
• Oregon -2.5 (-120) @ USC; Total 62.5 (-110)
• LSU -9.5 (-115) vs Texas A&M; Total 52.5 (-110)
• Utah State -3.5 (+100) vs Troy; Total 48.5 (-110)
• Mississippi State -6.5 (-110) vs Missouri; Total 58.5 (-110)
• Arkansas -6.5 (-120) vs Tulsa; Total 52.5 (Under -115)
• UMass -5.5 (-110) vs Sacramento State; Total 48.5 (-110)
• Air Force -5.5 (-105) @ Nevada; Total 49.5 (Under -115)
• Georgia Tech -3.5 (-105) vs Stanford; Total 47.5 (Over -115)
• Washington -9.5 (-120) vs Minnesota; Total 45.5 (-110)

College Football Week 4 best bet: Florida Gators -2.5 over Ole Miss Rebels (-124)

Odds courtesy of FanDuel Sportsbook at the time of publishing. Playable to -3 (-125). 

This time last week, I recommended betting LSU against this Ole Miss team. Obviously, that didn’t work very well, as the energy and emotion in Oxford – as well as some excellent football – led the Rebels to a win over their former coach. I thought they’d be a little too hyped up for that game, and while they did blow a lead, the Rebels managed to seal the deal and can now move on from the whole Lane Kiffin saga. 

There was so much attention, emotion and adrenaline surrounding last week’s contest between LSU and Ole Miss, and that presents a bit of a hangover spot for the Rebels this week when they travel to a true road game for the first time this season. It just so happens their destination, The Swamp in Gainesville, Florida, can be one of the most difficult venues to play in the conference when Gators fans have something for which to cheer – which they certainly do this year. Florida is off to an impressive 3-0 start, including a road win at Auburn last week and 162 total points scored this season. 

For what it’s worth, Florida has a massive edge in the analytical department, though it’s worth mentioning their schedule has one less power-conference opponent on it than Ole Miss. Still, the Gators are top-10 in offensive PPA and top-35 in defensive PPA outside of garbage time this season, while the Rebels are outside the top 30 and top 110, respectively, in those metrics. Give me the Gators to roll at home in what amounts to a big get-up spot for them and a hangover spot for Ole Miss.