Virginia Cavaliers vs. Louisville Cardinals Picks and Prediction for Saturday, October 4, 2025

A pair of ACC programs take to the field looking to pick up a win in the Bluegrass State when the #24 Virginia Cavaliers travel to face the Louisville Cardinals Saturday afternoon and we have you covered with our Virginia vs. Louisville prediction. Virginia upset #8 Florida State 46-38 in double overtime at home in their previous contest last Friday, winning outright as a seven-point underdog. Louisville rallied to drop Pitt 34-27 on the road last Saturday, covering the line as a three-point favorite in their previous game. In the all-time series between the teams, the Cardinals own an 8-5 advantage and have won the last three meetings, including a 24-20 road win in the most recent meeting on October 12, 2024. Read more about this Virginia vs. Louisville prediction! Don’t get penalized! Increase your bankroll with our NCAAF Betting Picks!

Virginia Trying to Avoid Letdown After Home Upset

Virginia won their third straight game as it survived #8 Florida State in double overtime at home last Friday and looks to maintain that momentum here. The Cavaliers improved to 4-1 overall and 2-0 in ACC play on the year as they look to try to avoid a letdown. Against Florida State, Virginia led 7-0 after the opening quarter and 14-0 in the second quarter, only to find themselves even at 21 at the half. The Cavaliers led in the final minute of regulation only to give up the tying score with 36 seconds remaining. After the teams traded field goals in the first overtime, Virginia scored a touchdown plus the two-point conversion in the second overtime. Their defense then stepped up, picking off Thomas Castellanos on the ensuing possession to secure the win. Virginia was outgained 514-440 in total offense despite winning the first down battle 27-24 and holding a 31:57 to 28:03 margin. Both teams committed three turnovers in the contest.

The Cavaliers are 22nd in the nation in passing offense with 296.2 yards per game, while they are 12th in rushing offense with 243.4 yards per contest on the ground. Virginia is 8th in the FBS in scoring offense with 45.6 points per game, while they are 69th in scoring defense by allowing 23.2 points per contest. Chandler Morris is 111 of 155 passing for 1,279 yards with 10 touchdowns and four interceptions while adding 169 yards and four scores on the ground. Daniel Kaelin (12 of 24, 194 yards, TD, INT, four rush yards) and Cole Geer (two of two, eight yards, 15 rush yards) are next up on the depth chart. J’Mari Taylor leads the team with 75 carries for 397 yards and seven scores this year. Harrison Waylee (30 carries, 229 yards, four TD), Xavier Brown (42 carries, 206 yards, TD) and Noah Vaughn (22 carries, 170 yards) are also effective in the run game. Cam Ross leads the team with 24 catches for 286 yards and a score this season. Trell Harris (21 receptions, 366 yards, three TD), Jahmal Edrine (19 grabs, 214 yards, TD), Dakota Twitty (11 receptions, 129 yards) and Kameron Courtney (eight catches,104 yards) are over the century mark in receiving yards. Will Betridge has hit all 28 extra point attempts and eight of 11 field goal attempts with a long of 41 this season.

Punter Daniel Sparks is questionable for this contest. Offensive linemen Brady Wilson, David Wohlabaugh Jr. and Wallace Unamba are all expected to be out here.

Cardinals Seeking to Remain Unbeaten

Louisville got off to a slow start against Pitt on the road but rallied to pick up the win to maintain its perfect record. The Cardinals improved to 4-0 on the season overall and are 1-0 in ACC play on the year. Against Pitt, Louisville found themselves in a 17-0 hole after the opening quarter, rallied to tie the game and trailed 27-17 at the half. The Cardinals’ defense stiffened in the second half, holding the Panthers scoreless, and the offense put up 17 points, including the winning touchdown with 7:03 remaining, for the victory. Louisville owned a 392-339 advantage in total offense, held a 23-14 margin in first downs and dominated time of possession by a 39:22 to 20:38 margin in the contest. Perhaps most important was the turnover department as the Cardinals recorded five takeaways while only committing one giveaway, though it was a pick-six.

The Cardinals enter this contest averaging 279 yards per contest through the air (29th in the nation) and 130.3 yards per game (103rd) on the ground this season. Louisville is 24th in the FBS by averaging 38.3 points per contest while the team is 37th in scoring defense by giving up 18.8 points per game. Miller Moss is 86 of 131 passing for 1,029 yards with five touchdowns and three interceptions plus a pair of rushing scores. Brady Allen (six of nine, 69 yards, TD, INT) and Deuce Adams (three of four, 18 yards, four rush yards) are next up on the depth chart. Isaac Brown leads the run game with 33 carries for 268 yards and three scores. Keyjuan Brown (22 carries, 110 yards, three TD), Braxton Jennings (12 carries, 70 yards, TD) and Duke Watson (23 carries, 62 yards) are also in the mix. Chris Bell leads the Cardinals with 23 receptions for 332 yards and two scores. Caullin Lacy (22 catches, 266 yards), Dacari Collins (six grabs, 105 yards) and Jaleel Skinner (eight receptions, 102 yards, TD) are each over the century mark in receiving yards. Cooper Ranvier is 13 of 13 on extra point attempts and seven of seven on field goal attempts with a long of 48 this year. Nick Keller is one of two on extra points and two of three on field goal attempts with a long of 57 on the season.

Running backs Keyjuan Brown, Jamarice Wilder and Shammai Gates are each questionable for this contest.

Virginia vs. Louisville Prediction

Spread Pick for Virginia vs. Louisville

• Louisville -6.5 (4 units)

Both teams are off to strong starts this year, but this game has striking similarities to last season. In 2024, Virginia came into the Louisville game 4-1 after downing Boston College, only to lose at home to the Cardinals. The Cavaliers have played just one road game this season and fell 35-31 at NC State last month. Louisville has won all three of their home games by double digits this season. The Cardinals have been good at taking the ball away, recording nine takeaways while limiting opposing offenses to 268.3 yards of total offense. Louisville should be able to take advantage of a soft Virginia defense to win this one by at least a touchdown, covering the line.

Over/Under Pick for Virginia vs. Louisville

• Under 62 (4 units)

These teams have been involved in some high-scoring affairs this season, but don’t be fooled. Virginia has gone over the number in each of their five games this season as their offense has scored at least 48 points in four games. They are going to have a tougher time moving the ball and putting points on the board against a stout Louisville defense. Louisville is giving up less than 19 points a game, limiting their first three foes to 17 points or less before Pitt put up 27 last week. Seven of the last 10 meetings between the schools have fallen short of the mark. Given the Cardinals’ ability to stunt drives with turnovers, expecting a ton of offensive fireworks is too much to ask here. Take the under as 31 points should be more than enough to win here.