The Week 6 college football odds board is loaded with high-profile matchups that could have potential College Football Playoff implications. Among the notable Week 6 college football betting lines is No. 10 Alabama (-10.5, 55.5) vs. No. 16 Vanderbilt, No. 18 Florida State vs. No. 3 Miami (-4.5, 54.5), No. 9 Texas (-6.5, 43.5) vs. Florida, Boise State vs. No. 21 Notre Dame (-18.5, 64.5), and No. 11 Texas Tech (-10.5, 50.5) vs. Houston. The biggest Week 6 college football spread sees the Oklahoma Sooners as 45.5-point favorites at home over the Kent State Golden Flashes.
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 6 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. 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 5 and evaluated each matchup. You can head to SportsLine to see every pick.
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Top college football predictions for Week 6
One of the top college football picks Marshall is recommending for Week 6: He’s backing Vanderbilt (+10.5) to stay within the spread at home against Alabama at Bryant-Denny Stadium in Tuscaloosa at 3:30 p.m. ET on Saturday. He also likes the Over (55.5) to hit.
Alabama (3-1) was blown out in its season opener, losing to Florida State 31-17 in Tallahassee. The Tide has rebounded with three straight wins, including a 24-21 victory over Georgia in Week 5. Vanderbilt (5-0) has won all five of its games in 2025 in blowout fashion, including a 31-7 statement win over South Carolina. Transfer quarterback Diego Pavia has been outstanding, throwing for 1,211 yards, 13 touchdowns, and three interceptions, and rushing for 294 yards and two scores.
“The Commodores of course scored that mighty 40-35 upset of the Tide last year for first series win since 1984,” Marshall said. “Vandy is 12-5 vs. line since last season, and also boasts the arrival of NMSU transfer Diego Pavia, who is 10-2 as dog since last season. Tide has won and covered three straight since FSU loss and has actually covered last five at Tuscaloosa. Vandy is on a 6-2 Over run since late 2024. Tech edge goes to Vanderbilt and the Over, based on recent and totals trends.” Go to SportsLine to see all of Marshall’s picks.
How to make college football picks for Week 6
Marshall has evaluated every other matchup and he’s found a critical 7-0-1 ATS trend in another Week 6 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 this week? 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 season, and find out.
College football odds for Week 6 notable games
See full Week 6 college football picks, odds, predictions here
(odds subject to change)
Saturday, October 4
Kentucky vs. Georgia (-20.5, 48.5)
Wisconsin vs. Michigan (-16.5, 42.5)
Florida vs. Texas (-6.5, 43.5)
Vanderbilt vs. Alabama (-10.5, 55.5)
Boise State vs. Notre Dame (-20.5, 65.5)
Virginia vs. Louisville (-7.5, 62.5)
Houston vs. Texas Tech (-11.5, 50.5)
Minnesota vs. Ohio State (-23.5, 44.5)
Florida State vs. Miami (-4.5, 54.5)
Mississippi State vs. Texas A&M (-14.5, 57.5)
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