Five undefeated CFB teams most likely to lose in Week 6

Entering October, 20 undefeated teams remain in FBS. That number will shrink this weekend, but by how much?

Here are five programs most vulnerable to losing their first game of the season in Week 6.

Note: All games on Saturday unless otherwise specified.

5. Louisville Cardinals (4-0, 1-0 in ACC)

vs. Virginia Cavaliers (4-1, 2-0 in ACC) • 3:30 p.m. ET, ESPN2

Associated Press No. 24 Virginia looks to knock another team from the unbeaten ranks following Week 5’s win over Florida State. The Cardinals’ defense, which is allowing an average of 18.8 points and 268.3 yards per game, will face its stiffest test. Virginia is second in the ACC in scoring, averaging 45.6 points per game. The Cavaliers start fast, with quarterback Chandler Morris third in the country in first-half passing yards, averaging 189.2 yards in the first two quarters. (h/t CFB Stats)

Louisville leads the all-time series 8-5, including three straight wins, but Saturday will mark the first time it’s played a ranked Virginia team. With a ninth victory, the Cardinals will set up a massive Week 8 game at Miami, which has its own hurdle this weekend.

4. Miami Hurricanes (4-0)

at Florida State Seminoles (3-1, 0-1 in ACC) • 7:30 p.m. ET, ABC

No. 18 Florida State’s loss to Virginia took some of the luster out of this classic rivalry, but it’s capable of pulling off the home upset over No. 3 Miami, which is currently a 3.5-point favorite, per ESPN BET. The 2025 game will mark the first in the rivalry since 2016, when both programs entered ranked. The Hurricanes have lost their past five matchups, dating back to 2005.

The Seminoles have the country’s top scoring offense (53 points per game), driven by their big-play ability. Florida State has produced 13 plays of at least 40 yards, the most in FBS. Miami’s defense is stout, but if Florida State can keep things close, one big play can swing the outcome of the game. 

3. Maryland Terrapins (4-0, 1-0 in Big Ten)

vs. Washington Huskies (3-1, 0-1 in Big Ten) • 3:30 p.m. ET, Big Ten Network

Per CFB Stats, in two starts against FBS teams with a winning record, Washington quarterback Demond Williams Jr. ranks first in FBS in passer rating, going 34-of-41 (82.9 percent) for 471 yards (11.5 yards per attempt) and four touchdowns. Maryland true freshman quarterback Malik Washington has been outstanding through four starts, but the Terrapins’ inability to run the ball — they average 3.3 yards per carry — could make it challenging for him to keep up with his counterpart on the opposite sideline.

2. Vanderbilt Commodores (5-0, 1-0 in SEC)

at Alabama Crimson Tide (3-1, 1-0 in SEC) • 3:30 p.m. ET, ABC

No. 10 Alabama has been on a tear since losing in Week 1 to Florida State, averaging 45 points per game in its past three games. The Commodores might be able to exploit a weak Tide rush defense, which allowed 457 yards against the Seminoles and Georgia Bulldogs. Still, we expect Alabama to be better prepared to stop No. 16 Vanderbilt’s offense than in last season’s stunning 40-35 loss, especially with the game in Tuscaloosa, where the Tide haven’t lost to Vanderbilt since 1984.

1. Houston Cougars (4-0, 1-0 in Big 12)

vs. Texas Tech Red Raiders (4-0, 1-0 in Big 12) • 7 p.m. ET, ESPN

Houston has already matched last year’s win total heading into the biggest game of the Willie Fritz era at home against No. 11 Texas Tech. The last time we saw the Red Raiders, they easily dispatched Utah on the road, 34-10, and they’re expected to handle the Cougars as well, with ESPN Analytics giving them a 74.5 percent chance to win and improve to 5-0. 

Other undefeated teams in action:

No. 1 Ohio State Buckeyes (4-0, 1-0 in Big Ten) vs. Minnesota Golden Gophers (3-1, 1-0 in Big Ten) • 7:30 p.m. ET, NBC/Peacock

No. 5 Oklahoma Sooners (4-0, 1-0 in SEC) vs. Kent State Golden Flashes (1-3, 0-1 in MAC) • 4 p.m. ET, SEC Network

No. 6 Texas A&M Aggies (4-0, 1-0 in SEC) vs. Mississippi State Bulldogs (4-1, 0-1 in SEC) • 7:30 p.m. ET, SEC Network

No. 14 Iowa State Cyclones (5-0, 2-0 in Big 12) at Cincinnati Bearcats (3-1, 1-0 in Big 12) • 12 p.m. ET, ESPN2

No. 23 BYU Cougars (4-0, 1-0 in Big 12) vs. West Virginia Mountaineers (2-3, 0-2 in Big 12) • Friday, 10:30 p.m. ET, ESPN

Memphis Tigers (5-0, 1-0 in American) vs. Tulsa Golden Hurricane (2-3, 0-2 in American) • 8 p.m. ET, ESPNU

Navy Midshipmen (4-0, 3-0 in American) vs. Air Force Falcons (1-3, 0-3 in MWC) • 12 p.m. ET, CBS/Paramount Plus

UNLV Rebels (4-0) at Wyoming Cowboys (2-2) • 7 p.m. ET, CBS Sports Network

Undefeated teams on a bye: No. 2 Oregon Ducks, No. 4 Ole Miss Rebels, No. 8 Indiana Hoosiers, No. 17 Georgia Tech Yellow Jackets, No. 19 Missouri Tigers, North Texas Mean Green