College football picks, predictions against the spread for Week 4, including USC-Michigan, Tennessee-Oklahoma

Four enticing matchups between AP Top 25 teams highlight the Week 4 college football schedule. 

That action starts Friday with a matchup of surprise unbeaten Big Ten teams. No. 24 Illinois travels to No. 22 Nebraska for an 8 p.m. ET matchup. Which team improves to 4-0? 

No. 11 USC makes its Big Ten debut at Michigan Stadium at 3:30 p.m. ET on Saturday. The Trojans (2-0) had a bye week, and No. 18 Michigan will look to avoid a second September loss at the Big House. 

The Big 12 comes into focus with a showdown between No. 12 Utah and No. 14 Oklahoma State in a battle of 3-0 teams. The Utes and Cowboys are looking to take control of the conference race. Kickoff is scheduled for 4 p.m. ET. 

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That bullds up to a prime-time matchup between No. 6 Tennessee (3-0) and No. 15 Oklahoma (3-0) at 7:30 p.m. ET. The Vols will look to score a second victory against a ranked opponent, and the Sooners are making their SEC debut. 

There are 18 games involving ranked FBS teams in Week 4. A look at our track record this season: 

• Straight up: 41-8 (15-0 in Week 3)
• Against the spread: 27-22 (11-4 in Week 3) 

Here are our picks against the spread for Week 4: 

College football Week 4 picks against the spread

Friday, Sept. 20 

• No. 24 Illinois at No. 22 Nebraska (-9) (8 p.m., Fox)

Nebraska beat Illinois 20-7 on the road last season. The Illini had just 21 rushing yards in that loss. Illinois has a +8 turnover margin, but Nebraska freshman quarterback Dylan Raiola (73.8% completion percentage) has just one INT in three starts. If Nebraska does not turn the ball over, it should pull away. Illinois is 9-3 ATS as a road underdog under Bret Bielema, so this requires betting through the trend.

Pick: Nebraska wins 28-17 and COVERS the spread. 

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Saturday, Sept. 21

• NC State at No. 21 Clemson (-16.5) (12 p.m., ABC) 

NC State quarterback Grayson McCall has an unspecified injury, and this line could move depending on his status for Saturday's game. The last three games in this series have been decided by 10 points or less, and the Wolfpack won 24-17 last season. NC State, however, has not won at Clemson since 2002 and the quarterback concerns are not going to be easy to get through with the Tigers coming off a bye week. 

Pick: Clemson wins 31-17 but FAILS TO COVER the spread. 

• Marshall at No. 3 Ohio State (-39.5) (12 p.m., Fox) 

Ohio State had a bye week and has not allowed an offensive TD yet. The combination of Will Howard's efficient play and a running game with two running backs that average more than 7.0 yards per carry in TreVeyon Henderson and Quinshon Judkins will be tough to stop. Marshall had a bye week and averages 6.5 yards per rushing attempt, but the Buckeyes will get a few interceptions against an inconsistent passing attack. Will the Thundering Herd get in the end zone? The Buckeyes are 10-5-1 ATS at home since last season. 

Pick: Ohio State wins 48-6 and COVERS the spread. 

• Arkansas State at No. 20 Iowa State (-21) (2 p.m., ESPN+)

Iowa State had a bye week to prepare for the Red Wolves, who played Michigan tough into the second half in a 28-18 loss. Arkansas State struggles against the run, so this should be a breakout game for Cyclones running back Abu Sama. Iowa State lost to Ohio in 2023, so Matt Campbell is not going to take a Group of 5 school lightly here. It just doesn't feel like a blowout if Jaylen Raynor does not turn the ball over. 

Pick: Iowa State wins 35-17 but FAILS TO COVER the spread. 

• Miami, Ohio at No. 17 Notre Dame (-27) (3:30 p.m., NBC/Peacock) 

Notre Dame knows the assignment now. After the Week 2 loss to Northern Illinois, the Irish have to blow teams out the rest of the way. Miami has managed 11 points per game in losses to Northwestern and Cincinnati, and they allow 182.5 rushing yards per game on 5.6 yards per carry. The Irish should be able to have success with that around Riley Leonard, and Jerimiyah Love – who averages 8.0 yards per carry. The defense will force two turnovers, too, in front of the home crowd. The Irish won the last meeting 52-17 in 2017. 

Pick: Notre Dame wins 42-10 and COVERS the spread. 

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• Buffalo at No. 23 Northern Illinois (-14) (3:30 p.m., ESPN+)

Northern Illinois had a bye week to soak up the upset victory against Notre Dame, and the expectations will increase under coach Thomas Hammock. Ethan Hampton has thrived with mistake-free play so far (526 yards, six TDs, 0 INTs). Buffalo is an improved team under first-year coach Pete Lembo. The Bulls average just one turnover per game. These teams have not met since 2021. 

Pick: Northern Illinois wins 30-19 but FAILS TO COVER the spread. 

• No. 11 USC (-6) at No. 18 Michigan (3:30 p.m., CBS) 

This line has dropped a half-point at other sportsbooks, and it is always risky to give the home team points in a matchup between ranked teams. The Trojans, however, have a defined quarterback situation with Miller Moss, and USC has committed just one turnover. If he handles Michigan pressure early, he should be fine. The Wolverines, meanwhile, have an unsettled quarterback situation with Davis Warren and Alex Orji, and they have a -4 turnover ratio through three weeks. That is not a winning formula, even at home, especially if the Trojans' run defense holds up. 

Pick: USC wins 28-21 and COVERS the spread. 

• Kent State at No. 10 Penn State (-49) (3:30 p.m., Big Ten Network)

Who made Kent State's schedule again? The Golden Flashes lost 71-0 to Tennessee, and now they have to face a Nittany Lions' team that is coming off a bye week after a subpar showing in Week 2 against Bowling Green. Penn State will pick their score with a rushing attack that includes Nick Singleton and Kayton Allen – who combine to average seven yards per carry. The Nittany Lions might be close to this line at halftime, and we will see if James Franklin pulls up in the fourth quarter. 

Pick: Penn State wins 52-6 and FAILS TO COVER the spread. 

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• Georgia Tech at No. 19 Louisville (-10.5) (3:30 p.m., ESPN2) 

Here is a hidden gem on the schedule. Louisville beat Georgia Tech 39-34 last season. The Cardinals have a rushing attack that averages 263 yards per game in front of Tyler Shough, who ranks third in the ACC with a 188.4 passer rating. The Yellow Jackets will counter with a relentless running game with Haynes King. The line feels a little high, but the Cardinals are 7-2 ATS at home and 6-2 ATS as a home favorite under Brohm. 

Pick: Louisville wins 34-21 and COVERS the spread. 

• UCLA at No. 16 LSU (-23) (3:40 p.m. ABC) 

UCLA quarterback Ethan Garbers has a 54.1% completion percentage, and the Bruins average 3.5 yards per carry. That is a bad combination against LSU in Death Valley. The line has already ticked up a half point, and the Tigers are coming off an emotional victory at South Carolina. Still, there is real blowout potential here knowing LSU is 9-2 ATS as a home favorite under Brian Kelly. The Bruins beat the Tigers 38-27 in 2021. The Tigers return the favor and just beat the line. 

Pick: LSU wins 38-14 and COVERS the spread. 

• No. 12 Utah at No. 14 Oklahoma State (-2.5) (4 p.m., Fox) 

This is a fun Big 12 matchup. The Utes turned to quarterback Isaac Wilson last week, and they rely on a no-nonsense rushing attack behind Micah Bernard and Mike Mitchell. How do they respond on the road against the Cowboys? Oklahoma State has struggled to run the football, but veteran quarterback Alan Bowman averages 322.3 passing yards per game and has just one interception. The Utes are 1-3 S/U and 2-2 ATS as a road underdog since last season. The Cowboys are 5-1 S/U but 2-4 ATS as a home favorite in the same span. This is a true coin-flip game. 

Pick: Oklahoma State wins 31-26 and COVERS the spread. 

• Vanderbilt at No. 7 Missouri (-21) (4:15 p.m., SEC Network) 

The Tigers have won the last three meetings in the series, and the Commodores are a puzzling team to this point. Diego Paiva led an upset against Virginia Tech, but Vanderbilt lost a heart-breaker to Georgia State in Week 3. Vanderbilt has just one turnover this season, and that might allow them to hang around in the SEC opener. This is the third straight week we have picked against Missouri, which beat the Commodores 38-21 last season. Similar game here. 

Pick: Missouri wins 34-17 but FAILS TO COVER the spread. 

• South Florida at No. 8 Miami, Fla. (-17.5) (7 p.m., TBD)

Miami leads the FBS in yards per play, and Cam Ward is in the mix for the Heisman Trophy. South Florida played Alabama into the fourth quarter in Week 2, and Alex Golesh will be a candidate for Power 4 vacancies this offseason. The Bulls are 7-2 ATS as an underdog under Golesh, and that is worth noting against the Hurricanes. That said, this Miami offense is on a different level, and the Hurricanes have the best third-down defense in the FBS. It will be hard for South Florida to keep up in the second half at that rate. 

Pick: Miami wins 42--21 and COVERS the spread. 

• No. 6 Tennessee (-7) at No. 15 Oklahoma (7:30 p.m., ABC) 

This is another tough call. The Sooners are a ranked team making their SEC debut, and the line has dropped a half-point from its open. Oklahoma quarterback Jackson Arnold and Tennessee quarterback Nico Iamaleava will be the focus here. Arnold has been sacked nine times in three games, while Iamaleava has been sacked three times. If the Vols avoid turnovers and the running game gets going around Dylan Sampson, then that will spoil Oklahoma's party. The Sooners have been a home underdog once this century – and that was a 45-24 loss to Ohio State in 2016. Are the Vols that good? We'll find out. 

Pick: Tennessee wins 34-24 and COVERS the spread. 

• Bowling Green at No. 25 Texas A&M (-23) (7:30 p.m., SEC Network+) 

The Aggies are back in the AP Top 25, and Marcel Reed was a dual-threat playmaker against Florida with 178 passing yards, 83 rushing yards and three total TDs. Texas A&M has two running backs in Le'Veon Moss and Amari Daniels who average more than 5.0 yards per carry. Bowling Green had a bye week to prepare after giving Penn State fits. The Falcons have lost their last five games against Power 5 opponents by 19.4 points. This is the Aggies' third game against a MAC school. 

Pick: Texas A&M wins 38-16 but FAILS TO COVER the spread. 

• Georgia Southern at No. 5 Ole Miss (-35.5) (7:45 p.m., SEC Network) 

Lane Kiffin and Clay Helton meet in a matchup of former USC coaches. JC French leads an Eagles' attack that averages 35.7 points per game. The problem is Georgia Southern allows 29 points per game, and they are up against an Ole Miss offense that leads the FBS with 692 yards per game. They also haven't allowed a TD yet. Look for the Rebels to improve to 4-0 ATS despite another huge line. 

Pick: Ole Miss wins 56-14 and COVERS the spread. 

• UL-Monroe at No. 1 Texas (-44.5) (8 p.m., ESPN+)

Arch Manning vs. General Booty is the start we needed in Week 4. Manning averaged 22.7 yards per completion in place of Quinn Ewers last week, and the Longhorns might rely on a running game that averages 173.3 yards per game. The Warhawks are 2-0 under first-year coach Bryant Vincent. The Longhorns won 52-10 against UL-Monroe in 2022. Manning enjoys a fantastic start, but the Warhawks score late to cover the spread. 

Pick: Texas wins 49-7 but FAILS TO COVER the spread. 

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• No. 13  Kansas State (-7) at BYU (10:30 p.m., ESPN) 

A late-night battle of unbeaten Big 12 teams. The Cougars have a pair of road victories, and quarterback Jake Retzlaff is the team's passing and rushing leader. BYU allows just 3.4 yards per carry. Does that hold up against Avery Johnson and a physical Kansas State rushing attack that piles up 244.3 yards on seven yards per carry? The Wildcats were 0-4 ATS as a road favorite last season, and these teams haven't played since 1997. Kansas State's defense travels, and Johnson leads an impressive road victory. 

Pick: Kansas State wins 31-21 and COVERS the spread.