2025 college football Week 4 picks against the spread, odds, lines, trends: Expert reveals best bets

The Week 4 college football odds board has populated with dozens of games that unfold over the course of Thursday, Friday and Saturday. Among the notable Week 4 college football lines, Oklahoma is -6.5 against Auburn, Indiana is -4.5 against Illinois and Utah is -3.5 against Texas Tech.

How should you make college football picks for those games, and what are the best spread, total and money-line picks to include in college football best bets? Before locking in any Week 4 college football picks, be sure to see the college football betting guide from legendary Vegas handicapper Bruce Marshall. 

For years Vegas-based Marshall was synonymous with The Gold Sheet, the famous sports betting newsletter. He has also won various handicapping titles and also is working on several book projects. Marshall crushed his 2024 college football betting picks, going 64-43 and returning more than 16 units, finishing the season as SportsLine’s top expert. He enters Week 3 of this season on a 15-6 roll on his official college football spread picks. Anyone following could have seen huge returns. 

Now, using his Tech Corner technique that evaluates all the trends, Marshall has turned his attention to the latest college football odds for Week 4 and evaluated each matchup. Head here to see every pick.

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Top college football predictions for Week 4

One of the top college football picks Marshall is recommending for Week 4: Tennessee (-37.5) covers at home against UAB in a 12:45 p.m. ET kickoff on Saturday. Marshall also projects the Over (67.5) to hit.

Tennessee fell in overtime to Georgia in Week 3, but showed signs of being a legitimate College Football Playoff contender. The offense, especially, excelled with 41 points against a top-tier Georgia defense. 

“The Blazers were 0-5 as underdogs last season before slipping inside a three-TD line at Navy on September 6,” Marshall told SportsLine. “UAB went Over in the first three this season, and are now over 10-2-1 since early 2024. The Vols have covered the last four as chalk and last three when laying double digits, and are also Over in seven straight since late 2024.” Go to SportsLine to see all of Marshall’s picks. 

How to make college football picks for Week 4

Marshall has evaluated every other matchup and he’s found a critical 8-0 ATS trend in another Week 4 game. Get betting analysis for each matchup at SportsLine, and use promo code CHAMPIONSHIP to get your first month for $1.

So what college football picks can you make with confidence, and what alarming trend do you need to know about in one of the week’s biggest game? Check out the latest college football odds below, then visit SportsLine to see which teams to back, all from the legendary Vegas expert who has won multiple handicapping titles and went 64-43 last seasons, and find out.

College football odds for Week 4 notable games

See full Week 4 college football picks, odds, predictions here
(odds subject to change)

Thursday, Sept. 18

Rice vs. Charlotte (+3.5, 42.5)

Friday, Sept. 19

Tulsa vs. Oklahoma State (-12.5, 55.5)

Iowa vs. Rutgers (+2.5, 45.5)

Saturday, Sept 20

Texas Tech vs. Utah (-3.5, 57.5)

Tennessee vs. UAB (-38.5, 67.5)

Oregon State vs. Oregon (-35.5, 57.5)

Florida State vs. Kent State (+43.5, 55.5)

Auburn vs. Oklahoma (-6.5, 48.5)

Tulane vs. Ole Miss (-12.5, 60.5)

Notre Dame vs. Purdue (+26.5, 52.5)

Michigan vs. Nebraska (+1.5, 44.5)

Georgia Tech vs. Temple (+24.5, 52.5)

Missouri vs. South Carolina (+13.5, 46.5)

Miami vs. Florida (+7.5, 52.5)

Illinois vs. Indiana (-4.5, 52.5)

Vanderbilt vs. Georgia State (+26.5, 53.5)

Texas vs. Sam Houston (+41.5, 51.5)

USC vs. Michigan State (+16.5, 55.5)