Virginia Cavaliers vs Louisville Cardinals Prediction, Odds and Picks for Saturday, 10/04/25

We have an important ACC showdown on our hands this week as the Virginia Cavaliers will take on the Louisville Cardinals in a game between a couple of teams that are looking to shake things up in a conference that feels pretty wide open at the moment. From a situational perspective, this is about as good of a spot as you can find on the Week 6 slate, as Virginia is coming off a momentous upset victory over Florida State at home last week. Now, the Cavaliers are undefeated and receiving plenty of buzz before heading to a game against a Louisville side that I still believe is one of the best teams in this conference. Jeff Brohm’s team has been very strong at home in his tenure to this point, and this could certainly be a spot where Virginia is still a bit hungover from a game in which the Cavaliers were frankly a bit fortunate to win.

Even outside of the situational angle, this is still a game where the home side should hold some significant advantages. There’s no doubt that the Virginia offense has some real juice to it, and that was part of why I was all over the Cavaliers to cover the number as home underdogs a week ago. Chandler Morris has been around the block a few times and he’s an experienced quarterback that leads an offense that is putting up points at a very high rate, as the Cavaliers are a top 15 unit in passing success rate, 3rd and 4th down success rate and points per drive per CFB-Graphs. However, this Louisville defense is a bit underrated, with the Cardinals sitting inside the top 15 in points per quality drive, 3rd and 4th down success rate and quality drive rate allowed. Louisville is also a top 40 unit in havoc rate, meaning that it should be able to force Morris into some ill-advised throws that lead to turnovers, much like we saw a week ago. On the other side of the ball, Miller Moss and the Louisville offense is one that should see plenty of success against a Virginia defense that just surrendered more than 500 yards to Florida State a week ago, and currently sits at 89th in points per drive allowed on the season. I’ll lay the points with the home team on Saturday. 

Virginia vs Louisville prediction: Louisville -6.5 available at time of publishing. Playable to Louisville -7.

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