College Football Week 4 AI Predictions: ATS Picks & Score Projections for Top 25 Games

Week 4 brings conference play into focus, and the latest college football AI predictions feature projected scores and against-the-spread picks for 25 of the best games on the schedule.

Seven ranked-vs.-ranked matchups headline Saturday's slate, including No. 1 Texas visiting No. 14 Tennessee, No. 4 Ole Miss traveling to No. 21 Florida, and No. 20 Oregon facing No. 12 USC. No. 2 Georgia also hosts Oklahoma, while No. 23 Texas A&M visits No. 10 LSU.

The AI model considers performance through the opening three weeks, advanced metrics, injuries, roster strength, matchup advantages, home-field edge, and current market movement. All ATS picks below use Kalshi's college football spread markets as of Thursday, Sept. 24. 

Follow all of SBR's college football picks throughout the season and check the latest college football odds before kickoff.

College Football Week 4 AI predictions

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Northwestern at Indiana AI prediction

Indiana has barely been challenged during its 3-0 start, winning its first three games by a combined 145-16. Northwestern enters unbeaten as well, but Friday represents a massive increase in difficulty against the defending national champions. The Wildcats need to shorten the game and prevent Indiana from generating short fields, but the Hoosiers have considerably more explosiveness on both sides of the ball. The spread is substantial, yet Indiana has shown little hesitation putting overmatched opponents away once it creates separation.

ATS pick: Indiana -20.5

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Clemson at California AI prediction

Clemson's defense remains the more trustworthy unit, but the Tigers' offense has lacked consistency and is now operating with freshman quarterback Tait Reynolds. That makes a cross-country road trip to Berkeley more dangerous than the talent gap might suggest. California should be able to keep this relatively low-scoring and force Reynolds to repeatedly execute on long drives. Clemson still has enough defensive talent to create the decisive turnover or short field, but this projects much closer to a four-quarter battle than a comfortable Tigers victory.

ATS pick: Clemson -2.5

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Colorado State at UTSA AI prediction

Both teams enter at 2-1, but the matchup sets up much better for UTSA inside the Alamodome. The Roadrunners have the stronger overall offensive profile and should be able to create more explosive plays than Colorado State can consistently answer. CSU can keep the game manageable by staying ahead of the chains, but falling behind early would force an offense with limited margin for error into a difficult script. UTSA's advantage should become increasingly apparent after halftime, producing a comfortable double-digit victory.

ATS pick: UTSA -13.5

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San Diego State at Toledo AI prediction

This is one of the more interesting Group-of-Six matchups on Saturday. San Diego State can make things uncomfortable by keeping the game physical and limiting possessions, but Toledo has the cleaner offensive setup and home-field advantage. The Rockets shouldn't need to turn this into a shootout if they avoid negative plays and consistently create manageable third downs. San Diego State is capable of hanging around into the second half, but Toledo should gradually establish control and create enough separation for a one-touchdown win.

ATS pick: Toledo -3.5

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Illinois at Ohio State AI prediction

Ohio State remains one of the most talented teams in the country despite its one-point loss at Texas, and the Buckeyes responded by demolishing Kent State 59-3. Illinois is a significant step up in competition and has enough quality to avoid being completely overwhelmed, particularly if it protects the football. Ohio State should control the matchup and win comfortably, but asking the Buckeyes to clear nearly four touchdowns against a Big Ten opponent is aggressive. A 24-point victory still leaves Illinois inside the enormous Kalshi number.

ATS pick: Illinois +27.5

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Wake Forest at Louisville AI prediction

Louisville enters with momentum after beating SMU 41-31, while Wake Forest was competitive for long stretches in a 33-20 loss to Miami. Gio Lopez threw for 312 yards and three touchdowns in that defeat, showing Wake has enough offense to punish Louisville if the Cardinals make mistakes. Louisville still owns the stronger roster and home-field advantage, but Wake's ability to generate explosive plays makes a 13.5-point spread difficult to lay. The Cardinals win without completely running away from the Demon Deacons.

ATS pick: Wake Forest +13.5

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Texas at Tennessee AI prediction

Both teams enter 3-0, but Texas faces its toughest environment of the season at Neyland Stadium. Arch Manning has already led the Longhorns past Ohio State, though he was less convincing in last week's 30-6 win over UTSA. Tennessee has enough offensive firepower to force Texas to score throughout the afternoon, even with leading rusher DeSean Bishop's status worth monitoring. Texas has the better overall roster and gets the straight-up edge, but more than a field goal is valuable with Tennessee at home.

ATS pick: Tennessee +4.5

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UCLA at Maryland AI prediction

UCLA has started 3-0 and enters this matchup with considerable offensive momentum after hanging 52 points on Purdue. Maryland's home field should make this a much more difficult assignment, and the Terrapins have enough defensive talent to prevent another offensive explosion. Still, UCLA has shown more consistency finishing drives and should have the better chance to create explosive plays when the game opens up. With Kalshi asking the Bruins to lay less than a field goal, the road favorite is worth backing.

ATS pick: UCLA -1.5

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Notre Dame at Purdue AI prediction

Notre Dame has taken care of business through three weeks and enters after beating Michigan State 27-10. Purdue's offense showed life in a 52-38 loss to UCLA, but the Boilermakers now face a significantly better defense. The Irish should control both lines of scrimmage and create plenty of scoring opportunities, yet laying 27.5 on the road in an in-state rivalry leaves very little room for a late Purdue touchdown. Notre Dame wins easily, but a 25-point margin keeps the Boilermakers inside the number.

ATS pick: Purdue +27.5

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Boise State at Western Michigan AI prediction

Both teams enter at 2-1, but Boise State has faced the more demanding early-season schedule and should benefit from that experience on the road. Western Michigan can make this uncomfortable if it limits explosive plays and keeps the Broncos from playing with a lead, but Boise has the stronger overall roster and more paths to generating points. The Broncos' rushing attack should become increasingly effective as the game progresses, allowing them to build a double-digit margin rather than relying on a late possession.

ATS pick: Boise State -7.5

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Ole Miss at Florida AI prediction

Kalshi making Florida the favorite despite Ole Miss entering ranked No. 4 makes this one of the week's most intriguing markets. Trinidad Chambliss has emerged as a legitimate Heisman contender after accounting for three touchdowns in the Rebels' 32-24 win over LSU. Florida is also unbeaten and showed its offensive ceiling by scoring 44 at Auburn, so this shouldn't be easy. Still, Ole Miss has been more convincing against high-level competition, and getting points with the Rebels provides value in a game they can win outright.

ATS pick: Ole Miss +3.5

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TCU at UCF AI prediction

TCU deserves to be a slight favorite based on overall roster quality, but the matchup becomes much closer once UCF's home-field advantage is factored in. Both teams enter at 2-1, and the Knights have already shown they can make this matchup uncomfortable after beating TCU 35-34 in their last meeting. UCF's ability to play faster at home and force TCU to defend the entire field gives the Knights a legitimate path to the upset. Getting more than a field goal makes the home side particularly appealing.

ATS pick: UCF +3.5

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Iowa at Michigan AI prediction

This matchup sets up as a defensive battle, but Michigan has the more trustworthy offensive path at home. Iowa has officially named Hank Brown its starting quarterback, adding another variable before a difficult trip to Ann Arbor. The Hawkeyes' defense can keep this close early, but Michigan should be able to create more favorable field position and eventually wear Iowa down. A low total doesn't necessarily prevent separation if one side consistently wins the field-position battle, and Michigan looks capable of turning this into a comfortable two-touchdown victory.

ATS pick: Michigan -5.5

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Utah at Iowa State AI prediction

Utah's defense has been outstanding, following a 43-10 win over Arkansas by shutting out Utah State 33-0. Iowa State presents a tougher road environment, but the Cyclones have already struggled to consistently generate offense against quality defenses. Utah doesn't need to turn this into a shootout if it continues controlling the line of scrimmage and producing short fields. Iowa State should hang around initially, but the Utes' physical advantage should become more pronounced over four quarters and produce another convincing win.

ATS pick: Utah -9.5

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Oklahoma at Georgia AI prediction

Oklahoma's defense has kept the Sooners competitive, allowing no opponent to score more than 17 points, but the offense remains a concern after a 14-6 win over New Mexico followed a loss at Michigan. Georgia has encountered no such problems, beating Arkansas 45-17 in its SEC opener. The Sooners should make the Bulldogs work harder than their previous opponents, particularly early, but Georgia's depth and ability to control the line of scrimmage should eventually create separation. Athens is a difficult place for a struggling offense to suddenly find answers.

ATS pick: Georgia -13.5

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Vanderbilt at Auburn AI prediction

Vanderbilt's 3-0 start makes the Commodores difficult to dismiss as a substantial road underdog. Auburn has more overall talent and should be able to generate pressure at Jordan-Hare Stadium, but the Tigers have already shown enough inconsistency to make laying nearly double digits uncomfortable. Vanderbilt can stay competitive by protecting the football and keeping Auburn from creating short fields. The Tigers get the straight-up prediction thanks to their advantage at home, but this looks much closer to a one-score SEC matchup than a runaway.

ATS pick: Vanderbilt +9.5

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Wisconsin at Penn State AI prediction

Penn State has started 3-0 and comes into its Big Ten opener after a dominant performance against Buffalo. Wisconsin is 2-1 and should provide a much more physical challenge, but the Badgers need to manufacture consistent offense against a Nittany Lions defense that hasn't given up many easy possessions. Penn State also owns the more reliable quarterback situation and a significant home-field advantage in Happy Valley. Wisconsin can keep this relatively close through halftime before Penn State's depth produces separation in the final two quarters.

ATS pick: Penn State -9.5

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Nebraska at Michigan State AI prediction

Nebraska has rolled through its first three games, averaging more than 46 points while committing only one turnover. The level of competition hasn't been particularly strong, but the Huskers have consistently done what good teams should against weaker opponents. Michigan State enters 2-1 after losing 27-10 at Notre Dame and now faces another team capable of controlling the line of scrimmage. East Lansing makes this a tougher test for Nebraska, but the Huskers' offensive efficiency should be enough to turn a competitive first half into a double-digit victory.

ATS pick: Nebraska -6.5

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James Madison at Old Dominion AI prediction

James Madison is 3-0 and deserves to be favored, but the Royal Rivalry usually gives Old Dominion an added edge at home. ODU has struggled to consistently finish drives, yet its defense should be able to prevent James Madison from creating the kind of separation required to comfortably cover nearly a touchdown. The Dukes have the stronger roster and should eventually make the decisive plays, but this projects as a possession-by-possession game that remains unsettled deep into the fourth quarter. Taking the home underdog is the better ATS position.

ATS pick: Old Dominion +5.5

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Oklahoma State at West Virginia AI prediction

Oklahoma State already owns one of the season's biggest upsets after knocking off Oregon, so West Virginia can't expect an easy night. The Cowboys have shown they can create explosive plays, but Morgantown presents a very different road environment and West Virginia should be able to make this more physical. The Mountaineers' ability to control possession and limit Oklahoma State's total number of drives is the key. With Kalshi asking West Virginia to lay less than a field goal, the home side has enough of an edge to cover comfortably.

ATS pick: West Virginia -1.5

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South Carolina at Alabama AI prediction

Alabama's offense looked dangerous in a 50-36 win over Florida State, while South Carolina enters after allowing 41 points in a home loss to Mississippi State. The Gamecocks have enough offensive talent to prevent Alabama from completely controlling the game, but stopping the Crimson Tide for four quarters is a much tougher task. Alabama should be able to exploit South Carolina's issues defending explosive plays and create a two-score advantage once the game opens up. The 11.5-point Kalshi spread is large, but the matchup supports it.

ATS pick: Alabama -11.5

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Kansas State at Cincinnati AI prediction

Both Kansas State and Cincinnati enter their Big 12 opener at 3-0, which makes nearly a touchdown a difficult number to lay on the road. Kansas State has the stronger overall profile and gets the straight-up prediction, but Cincinnati has been excellent at Nippert Stadium and should benefit from another night kickoff. The Bearcats don't need to control the matchup to provide value; they simply need to prevent Kansas State from consistently producing short fields. This looks like a one-possession conference game throughout.

ATS pick: Cincinnati +6.5

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Oregon at USC AI prediction

Oregon hasn't looked like the dominant team many expected entering the year. The Ducks needed a close game to beat Boise State and were then upset by Oklahoma State, while USC continues producing points behind Jayden Maiava. The Trojans' defense remains vulnerable enough that Oregon should have success offensively, but USC's home-field advantage and explosive passing game make this a difficult spot for the road favorite. This has legitimate shootout potential, and getting more than a field goal with USC creates value in a matchup the Trojans can win outright.

ATS pick: USC +2.5

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Texas A&M at LSU AI prediction

Both teams are coming off disappointing Week 3 losses, but Texas A&M's 31-21 home defeat to Kentucky is particularly concerning ahead of a trip to Death Valley. LSU struggled to slow Ole Miss but still has a significant defensive advantage in this matchup and should be able to pressure the Aggies into obvious passing situations. Texas A&M has enough talent to remain competitive early, but LSU should be able to lean on its defense and home-field advantage as the game progresses. A two-touchdown Tigers win is realistic.

ATS pick: LSU -8.5

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Missouri at Mississippi State AI prediction

Both teams enter 3-0, but Mississippi State has been the more convincing side against quality competition. Kamario Taylor threw for 251 yards and four touchdowns in the Bulldogs' 41-34 road win over South Carolina, while Missouri needed a much less explosive offensive performance to get past Troy 27-17. Starkville provides Mississippi State another advantage, and Taylor's mobility creates a difficult matchup for the Tigers' defense. Missouri can stay competitive early, but Mississippi State has enough offensive upside to build a double-digit margin.

ATS pick: Mississippi State -6.5

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