College Football Week 5 AI Predictions: ATS Picks & Score Projections for Top 25 Games

Conference play takes center stage in Week 5, and our latest college football AI predictions feature projected scores and against-the-spread picks for every game involving an AP Top 25 team.

Three ranked-vs.-ranked matchups headline Saturday's slate, including No. 5 Ohio State visiting No. 14 Iowa, No. 7 Alabama traveling to No. 16 Mississippi State, and No. 8 Florida facing No. 25 Missouri. No. 4 Miami also visits Clemson, while No. 10 BYU hits the road to face TCU.

The AI model weighs performance through the opening four 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, Oct. 1. 

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

College Football Week 5 AI predictions

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Boston College at SMU AI prediction

SMU owns the stronger overall roster and should have the offensive advantage at home, but laying more than 20 points in a conference matchup is still a demanding number. Boston College doesn't need to consistently match the Mustangs score-for-score if it can limit explosive plays and avoid giving SMU short fields.

The Mustangs should control the game and win comfortably, but a 17-point margin leaves Boston College safely inside the large Kalshi spread.

ATS pick: Boston College +20.5

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Notre Dame at North Carolina AI prediction

Notre Dame continues to look like one of the country's most complete teams after dismantling Purdue 49-10 on the road in Week 4. North Carolina now faces an Irish team capable of controlling both lines of scrimmage and creating scoring opportunities without needing to rely exclusively on explosive plays.

The number is significant on the road, but Notre Dame has enough advantages on both sides of the ball to build separation and maintain it into the fourth quarter.

ATS pick: Notre Dame -21.5

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Alabama at Mississippi State AI prediction

Alabama enters Starkville after dominating South Carolina 49-18, but Mississippi State is one of the biggest risers in the latest AP poll after beating Missouri 31-24 to remain unbeaten. The Bulldogs have earned their No. 16 ranking and present a much more difficult road test than the Crimson Tide faced last week.

Alabama has the talent advantage and gets the straight-up edge, but Mississippi State should make this a four-quarter game. More than six points with the home underdog is valuable.

ATS pick: Mississippi State +6.5

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UCF at Houston AI prediction

Houston continues to build momentum after scoring 42 points at Georgia Southern and climbing to No. 20 in the new AP poll. The Cougars have shown enough explosiveness to punish defenses when they generate favorable field position, and returning home gives them another advantage against UCF.

UCF can keep this manageable early, but Houston should gradually create separation. A two-touchdown projected margin is enough to lay the double-digit number.

ATS pick: Houston -11.5

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Vanderbilt at Georgia AI prediction

Georgia reinforced its status as one of the nation's elite teams with a dominant 41-13 win over Oklahoma. The Bulldogs should control this matchup in Athens as well, particularly at the line of scrimmage, but Vanderbilt is getting a massive cushion in a conference game.

Georgia can establish a comfortable lead without necessarily keeping its foot on the gas for four quarters. A three-touchdown victory still keeps Vanderbilt inside the 24.5-point spread.

ATS pick: Vanderbilt +24.5

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Auburn at Tennessee AI prediction

Tennessee came within three points of upsetting No. 1 Texas in Week 4, and the Volunteers now return to Neyland Stadium for a more manageable conference matchup. The Vols have enough offensive firepower to attack Auburn vertically while also leaning on the running game if they establish an early lead.

Auburn should have stretches of success, but Tennessee is the more complete team and should eventually pull away. The Volunteers are worth laying just over a touchdown.

ATS pick: Tennessee -7.5

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Florida at Missouri AI prediction

Florida delivered one of Week 4's biggest statements by beating then-No. 4 Ole Miss by 24 points, sending the Gators from No. 21 to No. 8 in the AP poll. Missouri fell at Mississippi State but remains ranked, making this one of three Top 25 matchups on Saturday.

Playing in Columbia adds some risk for Florida, but the Gators' recent offensive form gives them the higher ceiling. They should generate enough scoring opportunities to clear the 5.5-point spread.

ATS pick: Florida -5.5

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Ohio State at Iowa AI prediction

Ohio State handled Illinois 42-19 in Week 4, but Saturday's trip to Kinnick Stadium represents a much different challenge. Iowa is unbeaten after winning 20-19 at Michigan on the final play, and the Hawkeyes have climbed to No. 14 in the country.

Ohio State has enough talent to escape with the victory, but Iowa's defense and home-field advantage should prevent this from becoming comfortable. The Hawkeyes stay within two touchdowns.

ATS pick: Iowa +14.5

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Kentucky at South Carolina AI prediction

Kentucky's strong start has pushed the Wildcats into the AP Top 25, while South Carolina returns home after being overwhelmed by Alabama. The Gamecocks are favored, but their offense will need to be much more efficient against a Kentucky team that has already shown it can handle difficult road environments.

This projects as one of Saturday's tighter SEC games. Kentucky has enough balance to stay inside the number and has a legitimate path to winning outright.

ATS pick: Kentucky +2.5

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BYU at TCU AI prediction

BYU enters Week 5 unbeaten and ranked No. 10, although a trip to Fort Worth represents one of the Cougars' more difficult assignments to date. TCU has enough offensive ability to make BYU defend the entire field, but the Cougars have been the more consistent team on both sides of the ball.

TCU should keep things competitive early before BYU's balance becomes more apparent after halftime. The Cougars pull away enough to cover the 6.5-point number.

ATS pick: BYU -6.5

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Washington at USC AI prediction

USC is looking to rebound after Oregon handed the Trojans their first loss of the season, 41-27. The defeat dropped USC to No. 18, and another capable opponent arrives with Washington having enough offensive talent to punish defensive breakdowns.

The Trojans should respond at home and have the better chance to win a high-scoring game, but 10.5 points is too much against a Washington team capable of keeping pace offensively.

ATS pick: Washington +10.5

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Miami at Clemson AI prediction

Miami has climbed to No. 4 after a dominant start, including a 52-3 victory over Central Michigan last week. Clemson has been far less convincing, but Death Valley remains a difficult place to lay more than 20 points against a roster with enough defensive talent to keep stretches of the game competitive.

The Hurricanes should win comfortably, but this number requires something close to another blowout. Clemson does enough defensively to stay within the massive spread.

ATS pick: Clemson +20.5

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Texas Tech at Colorado AI prediction

Texas Tech remains unbeaten after putting 49 points on Sam Houston, and the Red Raiders have risen to No. 12 in the AP poll. Their ability to create explosive plays on offense while generating turnovers defensively gives Colorado very little margin for error.

Playing in Boulder should keep Colorado competitive for stretches, but Texas Tech has too many ways to create separation. The Red Raiders are capable of winning this by multiple touchdowns.

ATS pick: Texas Tech -11.5

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Utah State at Boise State AI prediction

Boise State has entered the Top 25 after winning three straight games following its narrow loss at Oregon. The Broncos return home with a substantial offensive advantage against Utah State and should be able to establish control quickly if they avoid turnovers.

Laying more than 20 points always creates some late-game risk, but Boise State has the scoring ceiling to turn this into one of Saturday's more comfortable victories.

ATS pick: Boise State -20.5

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McNeese at LSU AI prediction

LSU rebounded from its loss to Ole Miss with an emphatic 35-6 victory over Texas A&M. The Tigers now face a major drop in competition against McNeese and should have a significant advantage at nearly every position.

LSU should be able to build an early lead and give its reserves plenty of work in the second half.

ATS pick: LSU -48.5

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Indiana at Rutgers AI prediction

Indiana remains unbeaten, but Northwestern provided its first serious scare of the season in a 29-23 game last Friday. The Hoosiers still sit No. 6 in the latest AP poll, but Saturday's 23.5-point spread asks them to dominate a conference opponent on the road.

Indiana should control the matchup and win comfortably, yet Rutgers can do enough to avoid a four-touchdown defeat. The Scarlet Knights are the better side of the enormous number.

ATS pick: Rutgers +24.5

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