2025 College Football Week 6

College football Saturday might as well be called “Upset Saturday.” Last weekend alone, there were four upsets involving a lower-ranked or unranked winner. Including a shocking win by Virginia over Florida State, ranked No. 8 going into Week 5.
No ranking is safe, and there’s no room to breathe on the path to the College Football Playoff (CFP). It feels like more upsets are to come in week 6. Here are the biggest NCAAF Week 6 odds coming this weekend.

Main Event Matchups

No. 14 Iowa State Cyclones (5-0) at Cincinnati Bearcats (3-1)

• Odds: Cincinnati -1.5
• Total: 54
• Time: 12 p.m. ET
• ESPN2

The Cyclones have been quietly climbing the College Football rankings. Efficiency has been key. Cyclones quarterback Rocco Becht has just two interceptions, contrasted with seven touchdowns and a 65.8% completion rate. Meanwhile, their defense has kept opponents to an average of 14.2 points per game.

Despite that, they’ve opened as +1.5 underdogs against Cincinnati. Likely due to Cincinnati QB Brendan Sorsby’s dominance on Saturdays. He’s been a dual threat all year, leading the Bearcats with 1,043 passing yards, 10 touchdowns, one interception, and a team-high 227 rushing yards. It seemed like the Bearcats’ AP Top 25 chances were ruined in a Week 1 loss to Nebraska, but a fourth straight win against an undefeated and ranked opponent could boost their position again.

No. 9 Texas Longhorns (3-1) at Florida Gators (1-3)

• Odds: Texas -6.5
• Total: 41.5
• Time: 3:30 p.m. ET
• ESPN

Arch Manning remains must-see TV: It began as a Heisman watch, and now it’s a disaster watch. Everyone enjoys seeing an overhyped prospect stumble, and that’s what’s happened to Manning in 2025. It adds an extra layer of interest to No. 9 Texas’s visit to unranked Florida. How will Manning perform against a defense that managed to stifle and intercept top-ranked quarterbacks like Miami’s Carson Beck and LSU’s Garrett Nussmeier?

Based on the odds, not much passing is anticipated. Florida, sitting at 1-3, is a conservative 6.5-point underdog at home, and the total is a surprisingly low 41.5. Oddsmakers don’t expect much offense, which could keep the Gators in the game into the fourth quarter.

No. 16 Vanderbilt Commodores (5-0) at No. 10 Alabama Crimson Tide (3-1)

• Odds: Alabama -10.5
• Total: 56
• Time: 3:30 p.m. ET
• ABC

When it comes to college football in the state of Tennessee, the Volunteers dominate the airwaves, with the Commodores a distant second. But that could change if they manage to upset the mighty Alabama Crimson Tide.

Vandy has been absolutely dominant on offense, averaging 49 points per game, which ranks them sixth in all of college football. QB Diego Pavia leads the high-scoring offence. He’s on the Heisman watch with 1,211 yards passing, 13 touchdowns, just three interceptions, and an 88.4 QB rating – third best in the country.

Alabama is going to have its hands full, but is coming off a dominant showing, holding Georgia QB Gunner Stockton to 130 yards in a 24-21 win that derailed his Heisman hopes.

No. 24 Virginia Cavaliers (4-1) at Louisville Cardinals (4-0)

• Odds: Louisville -6.5
• Total: 62
• Time: 3:30 p.m. ET
• ESPN2

How wild is the 2025 college football season? After Virginia upset Florida State 46-38 and ruined their CFP hopes, they could face an unranked Louisville. Oddsmakers already favour Louisville at home by 6.5 points.

Louisville’s balanced attack makes them dangerous, averaging 5.4 yards per carry and nearly 280 passing yards. That creates issues for Virginia, whose defense has struggled to stop both the run and pass, often giving up big plays that a team like Louisville is set to exploit.

Virginia’s offense is its best chance to stay competitive. Their rushing attack averages a 12th-best 243.4 yards per game, while Louisville’s defense gives up 117.5 yards per game on the ground.

No. 3 Miami Hurricanes (4-0) at No. 18 Florida State Seminoles (3-1)

• Odds: Miami -4
• Total: 53.5
• Time: 7:30 p.m. ET
• ABC

In the old college football setup, Florida State’s upset loss would have crushed all hopes of a major bowl game. However, in the NIL landscape, they need to move on and prepare for a big opportunity against the Hurricanes.

Florida State is just a four-point underdog at home versus No. 3 Miami. Oddsmakers understand that anything can happen in this ACC rivalry; the underdog is 7-3 against the spread (ATS) in the last 10 meetings.

Miami should also understand the gravity of the situation. They’ve moved up to No. 3 in the rankings, have an elite defense, and QB transfer Carson Beck has been as advertised. Now’s the time to make a serious run at the National Championship.

*Odds subject to change