Preview and Picks for NCAA Football Week 6

College football in October kicks off Week 6 action, and the 2025 college football games on Oct. 4 features two Top 25 matchups in the SEC and ACC. 

Time to turn it around following a 9-2 ATS run on Top 25 picks and opinions in Week 2 and Week 3. But last week's great games and Top 25 matchups between Oregon-Penn State and Alabama-Georgia was part of our poor picks and results. 

I'll be adding more picks and opinions later in the week following more stats and matchup analysis. Top 25 rankings, games and odds below and noted line moves and adjustments from college football Week 6 opening lines and totals. 

Notre Dame saw the biggest line move in Top 25 action from -16 to -20.5 vs. Boise State, and the total down 2 points. The Iowa State-Cincinnati game has seen the favorite flip towards the Bearcats. 

Top 25 Games and Week 6 Odds

Betting lines and college football odds from BetUS and top online sportsbooks refresh periodically and are subject to change, including on props and live betting. Current point spread on favorites plus game totals. All times ET. 

Check back by Friday each week as we add more Picks and Opinions with select analysis, stats and information you can bet on. 

Saturday, Oct. 4 

(One Top 25 team playing Friday, BYU)

No. 1 Ohio State (-24) vs. Minnesota, 44.5 | 7:30 pm | NBC
No. 2 Oregon | Bye 
No. 3 Miami (-4) at No. 18 Florida State, 53.5 | 7:30 pm | ABC  
No. 4 Ole Miss | Bye  
No. 5 Oklahoma (-45.5) vs. Kent, 53.5 | 4 pm | SEC Network
No. 6 Texas A&M (-14) vs. Mississippi State, 55.5 | 7:30 pm | SEC Network
No. 7 Penn State (-25.5) at UCLA, 50.5 | 3:30 pm | CBS
No. 8 Indiana | Bye 
No. 9 Texas (-7) at Florida, 42 | 3:30 pm | ESPN
No. 10 Alabama (-10.5) vs. No. 16 Vanderbilt, 55.5 | 3:30 pm | ABC
No. 11 Texas Tech (-11) at Houston, 51 | 7 pm | ESPN
No. 12 Georgia (-20.5) vs. Kentucky, 48.5 | 12 pm | ABC
No. 13 LSU | Bye
No. 14 Iowa State at Cincinnati (-2), 54 | 12 pm | ESPN2
No. 15 Tennessee | Bye 
No. 17 Georgia Tech | Bye
No. 19 Missouri | Bye
No. 20 Michigan (-17) vs. Wisconsin, 42.5 | 12 pm | FOX
No. 21 Notre Dame (-20.5) vs. Boise State, 62.5 | 3:30 pm | NBC
No. 22 Illinois (-10) at Purdue, 57 | 12 pm | Big Ten Network 
No. 23 BYU (-18.5) vs. West Virginia, 47 | 10:30 pm Friday, ESPN
No. 24 Virginia at Louisville (-7), 61.5 | 3:30 pm | ESPN2
No. 25 Arizona State | Bye

Only 3 teams received first place votes this week, Ohio State (46), Oregon (16) and Miami (4). 

Others receiving votes South Florida, Utah, Mississippi State, Memphis, Louisville, Southern Cal, Maryland, North Texas, TCU, UNLV. 

Other noteable games on Sat., Oct. 4 

- Clemson (-14) at North Carolina, 47
- Washington (-6.5) at Maryland, 62.5
- Michigan State at Nebraska (-11.5), 49
- Tulsa at Memphis (-20.5), 57
- Colorado at TCU (-14), 58
- Kansas State at Baylor (-6.5), 61.5
- Syracuse at SMU (-17), 58.5
- UNLV (-3.5) at Wyoming, 51.5

NCAA Football Week 6 Top 25 Picks

ESPN College GameDay will be in Tuscaloosa Saturday and on-air analyst and legendary Alabama coach Nick Saben will be honored during the first quarter by the College Football Hall of Fame and National Football Foundation.

The Vanderbilt villain will make his debut at Bryant-Denny Stadium this week https://t.co/Epd1G1y9AP

— Nick Kelly (@_NickKelly) September 30, 2025

Vanderbilt at Alabama 

The Commodores topped the Tide last year in Nashville 40-35, as a 24-point underdog. Fans were delirious, carrying the goal posts out of the stadium and two miles down Broadway to toss them into the Tennessee River. Now Vanderbilt (5-0) is undefeated as they tackle Alabama (3-1) again, and the Commodores took some early money from the opening line of Alabama -12 down to -10.5 with the game total holding at 55 points. Alabama enters off a road win at Top-5 Georgia 24-21 with QB Ty Simpson passing for 273 yards and 2 TD's - his 11th TD pass this season without an interception. Alabama ran 24 more plays than Georgia, but the 'Dawgs were able to average 6.7 yards per play on 357 total yards including 227 rushing. The Crimson Tide defense is allowing 274 yards per game against a stronger schedule than Vanderbilt, who is still top 26 allowing 315 ypg - same as A&M, LSU and Auburn. Alabama is averaging 444 yards per game on offense to Vanderbilt 499 ypg - top 10 in the country. But key for the 'Dores is the balanced attack rushing for 230 ypg and passing for 269 with duel QB Diego Pavia passing for more than 1200 yards, 9.6 yards per pass and 13 touchdowns (plus 2 rushing). Only 15 power conference teams are rushing for at least 200 yards per game, and eight of 230 ypg or more. Alabama is rushing for just 122 ypg, and taking the points with that stat profile is the prudent play. Opinion: Vanderbilt   

Miami at Florida State

Check back for other select games, analysis, picks and opinions with information you can bet on. 

You can bet on it. 

FairwayJay is a proven sports handicapper and loves college football. He's been handicapping and betting college football for more than two decades and is recognized as one of the sports industry's most insightful analysts. He chips in additional sports betting coverage and reporting on industry news and events. Follow FairwayJay here at OSGA.com and on X @FairwayJay for more sports and betting insights.