College football picks: Predictions against the spread, odds, betting lines for top 25 games in Week 4

Sep 25, 2026 at 4:02 pm ET • 5 min read

There's no time for apple picking this weekend.

If ever there was a weekend to be locked in front of your television all day, it's this Saturday. 

We have six – SIX – top 25 matchups alone. That's more than the first three weeks combined and the most in a single week in three years. College football is like pizza – if you aren't familiar, all pizza is still pretty good – but we still have to celebrate special weekends like this one. We've entered into the part of the season where the games really start to matter.

Like No. 23 Texas A&M at No. 10 LSU. As I wrote earlier this week, that game has all the makings of a loser-leaves-town impact. Both teams started the season as popular College Football Playoff picks and yet one will be 0-2 in conference play before even getting out of September. The data set is small but no team has ever started 0-2 in conference play and still made the playoff.

That's just one of four top 25 SEC matchups. 

You can kick the day off with No. 1 Texas at No. 14 Tennessee at noon ET. Is Arch Manning the guy we saw triumphantly guide the Longhorns to a second-half comeback over Ohio State or the guy who struggled against UTSA? It's a big game for Manning and a star-making opportunity for Tennessee true freshman quarterback Faizon Brandon.

No. 4 Ole Miss at No. 21 Florida might be the most intriguing game of the day. Fresh off a win over former coach Lane Kiffin, will Ole Miss suffer from an emotional hangover, or are the Rebels so good it doesn't matter? First-year head coach Pete Golding is saying all the right things, but escaping from The Swamp with a victory won't be easy. Having a guy like Trinidad Chambliss certainly helps, though.

Kamario Taylor, the other star quarterback in the state of Mississippi, gets a chance to keep the momentum going for No. 24 Mississippi State against No. 19 Missouri. A win over the Tigers would make the Bulldogs 4-0 headed into a huge home game against No. 8 Alabama.

Outside the SEC, we have two tasty Big Ten top-25 games. No. 17 Iowa travels to No. 18 Michigan in what could be a race to see which team can score 20 points first. Both teams sit on the periphery of the CFP race and could take a big step forward with a win on Saturday. 

And then there is No. 20 Oregon at No. 12 USC. The Ducks, a popular preseason title pick for some, already have a bad loss to Oklahoma State and can't afford to drop to 2-2 with what's still left on the schedule. Oregon coach Dan Lanning has already faced criticism for his coordinator hires, and that noise will only get louder with a loss in Los Angeles. For Lincoln Riley, it's time to prove the investment was worth it. The Trojans have a chance to make a real statement at home against Oregon and can't let that opportunity slip by. 

All times Eastern

No. 1 Texas vs. No. 14 Tennessee 

Noon on ABC, Fubo (try free): After watching its dramatic comeback against Ohio State, Texas looks like a legitimate national title contender, and this line is under a touchdown. That makes it tempting to pick the Longhorns, but the Volunteers remain a mystery. Their game against Georgia Tech was over rather early, so it's hard to gauge exactly what to expect from that squad. Because of that, the total is more appealing. I documented Manning's road struggles above, and I have to give the edge to the Texas defense in a matchup against a true freshman. Points may be at a premium for much of this game. Pick: Under 55.5

	Tom Fornelli	Chip Patterson	Brandon Marcello	John Talty	Richard Johnson	Shehan Jeyarajah	David Cobb	Brad Crawford	Chris Hummer
TEX -4.5	Texas	Tennessee	Tennessee	Texas	Texas	Texas	Tennessee	Texas	Texas
SU	Texas	Tennessee	Texas	Texas	Texas	Texas	Tennessee	Texas	Texas

No. 21 Florida vs. No. 4 Ole Miss 

3:30 p.m. on ABC, Fubo (try free): I'm a little skeptical of Florida being a favorite in this game, but I've no real interest in going after the spread here. No, the one thing I'm most confident about is that points will be scored. Florida's defense hasn't exactly been incredible despite playing a relatively easy schedule overall, and we've already seen Ole Miss allow points to Louisville and LSU. I think we get another shootout here. Pick: Over 58.5 -- Tom Fornelli

	Tom Fornelli	Chip Patterson	Brandon Marcello	John Talty	Richard Johnson	Shehan Jeyarajah	David Cobb	Brad Crawford	Chris Hummer
FLA -3.5	Florida	Ole Miss	Florida	Ole Miss	Ole Miss	Ole Miss	Ole Miss	Ole Miss	Ole Miss
SU	Florida	Ole Miss	Florida	Ole Miss	Ole Miss	Ole Miss	Ole Miss	Florida	Ole Miss

No. 18 Michigan vs. No. 17 Iowa 

3:30 p.m. on CBS CBSSports.com, CBS Sports App Paramount+ Premium: Michigan has been living on borrowed time the entire season, including the stunning Hail Mary against Western Michigan. Iowa will be the team to finally make them pay -- and ironically, it'll start on offense. Running back Kamari Moulton and wide receiver Tony Diaz give the program one of its best RB-WR combos of the past 20 years, and they will make just enough explosive plays to pull off the upset in the Big House. Pick: Iowa SU (+178) -- Shehan Jeyarajah

	Tom Fornelli	Chip Patterson	Brandon Marcello	John Talty	Richard Johnson	Shehan Jeyarajah	David Cobb	Brad Crawford	Chris Hummer
MICH -5.5	Iowa	Michigan	Michigan	Iowa	Iowa	Iowa	Michigan	Iowa	Iowa
SU	Michigan	Michigan	Michigan	Michigan	Michigan	Iowa	Iowa	Iowa	Michigan

No. 2 Georgia vs. Oklahoma 

3:30 p.m. on ESPN, Fubo (try free): The only quarterbacks in the Power Four more efficient than Gunner Stockton right now are Trinidad Chambliss at Ole Miss and Miami's Darian Mensah -- and no one's talking about the Georgia signal caller's electric start. And when you have one leader on offense in rhythm while the other team's guy is struggling this season from a confidence standpoint, it raises questions about Oklahoma's ability to hang in this matchup. This feels like a 31-7 type game unless the Sooners can get something going offensively for the first time all season against an opponent of substance. Pick: Under 43.5 points -- Brad Crawford

	Tom Fornelli	Chip Patterson	Brandon Marcello	John Talty	Richard Johnson	Shehan Jeyarajah	David Cobb	Brad Crawford	Chris Hummer
UGA -14	Georgia	Georgia	Oklahoma	Georgia	Georgia	Georgia	Georgia	Georgia	Oklahoma
SU	Georgia	Georgia	Georgia	Georgia	Georgia	Georgia	Georgia	Georgia	Georgia

No. 10 LSU vs. No. 23 Texas A&M

7:30 p.m. on ESPN, Fubo (try free): On the heels of an embarrassing home loss to Kentucky, Texas A&M is venturing into college football's most intimidating night atmosphere. It's the wrong place to be for a team that is grappling with shaky quarterback play. LSU has plenty of flaws, too, but the Tigers are salty enough defensively to make life hard on Marcel Reed. On the other side, A&M's defense never looked comfortable or disruptive against Kentucky. LSU coach Lane Kiffin should have a field day game-planning after watching that tape. Pick: LSU -7.5 -- David Cobb

	Tom Fornelli	Chip Patterson	Brandon Marcello	John Talty	Richard Johnson	Shehan Jeyarajah	David Cobb	Brad Crawford	Chris Hummer
LSU -8.5	LSU	LSU	Texas A&M	Texas A&M	LSU	LSU	LSU	Texas A&M	Texas A&M
SU	LSU	LSU	LSU	LSU	LSU	LSU	LSU	LSU	LSU

No. 12 USC vs. No. 20 Oregon 

7:30 p.m. on NBC, Fubo (try free): While the series between these two teams has slanted heavily in Oregon's favor, USC has not lacked for points against the Ducks. And while the oddsmakers have clearly identified the strength advantage for both teams, predicting a high-scoring game with their over-under total, it might still not be enough points. These two teams combined for 69 points in 2025 and 63 points in 2023, leaving some wiggle room with the current posted total. Pick: Over 61.5 -- Chip Patterson

	Tom Fornelli	Chip Patterson	Brandon Marcello	John Talty	Richard Johnson	Shehan Jeyarajah	David Cobb	Brad Crawford	Chris Hummer
ORE -3	Oregon	Oregon	USC	Oregon	Oregon	Oregon	Oregon	Oregon	Oregon
SU	Oregon	Oregon	Oregon	Oregon	Oregon	Oregon	Oregon	Oregon	Oregon

SportsLine's proven computer model has simulated every Week 4 college football game 10,000 times. Visit SportsLine now to see the picks, all from the model that's on a 22-19 run on top-rated CFB picks this season.