The Louisville Cardinals take on the Pitt Panthers in Pittsburgh, PA. Kickoff is set for 12 p.m. ET on ESPN2.
Louisville is favored by -4.5 points on the spread with a moneyline of -190. The total is set at 58 points.
Here’s my Louisville vs. Pitt prediction and college football picks for Saturday, September 27.
Louisville vs Pitt Prediction
- Louisville vs. Pitt Pick: Louisville -4.5 (Play to -6.5)
My Pittsburgh vs. Louisville best bet is on the Cardinals to cover the spread. Find the best line available on our live NCAAF odds page.
Louisville vs Pitt Odds
| Louisville Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
-4.5 -110 | 53.5 -110o / -110u | -190 |
| Pitt Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
+4.5 -110 | 53.5 -110o / -110u | +160 |
- Louisville vs Pitt point spread: Louisville -4.5
- Louisville vs Pitt over/under: 53.5 points
- Louisville vs Pitt moneyline: Louisville -190, Pitt +160
Louisville vs Pitt Preview
Louisville Cardinals Betting Preview: Good Matchup for Cards
Louisville enters this matchup at 3-0 with a balanced, efficient attack. The Cardinals rank 41st nationally in offensive success rate, a measure of how often plays stay on schedule. That consistency is key to controlling possessions and wearing down a defense.
Inside the red zone and on key scoring drives, Louisville is even better, sitting 37th in finishing drives (points per opportunity).
Their 36th ranking in offensive explosiveness shows the Cardinals can generate chunk plays even with a slower tempo (101st), which reflects deliberate control more than a lack of firepower.
The Cardinals aren’t one-dimensional. Their defense ranks 23rd in success rate, 19th in hard stops and 13th in average start field position allowed. They consistently win early downs and give the offense favorable field position.
This will be Miller Moss' first true test after transferring from USC. So far, he's been a solid quarterback, rocking an 81.3 PFF passing grade.
Look for him to push the ball downfield. His average depth of target at 9.7 yards is just behind known gunslinger Joey Aguilar's 9.9 average depth of target.
This could be a problem for a Pitt team with a propensity for giving up bigger plays.
Pitt Panthers Betting Preview: QB Won't Save Panthers
On paper, Pitt’s defense is impressive, as it's fourth in success rate, fourth in hard stops and top-30 in momentum kill rate. These numbers suggest a unit that wins on early downs and forces punts.
But context matters: Two of Pitt’s first three games came against soft opponents. Against their lone credible test — a mid-tier West Virginia team — the Panthers surrendered 31 points.
West Virginia is far from an offensive juggernaut, yet it exposed weaknesses in Pitt's explosive-play prevention (108th nationally in explosiveness allowed) and in the red zone.
When a defense built on consistency yields chunk plays, easy red zone chances and 30+ points to a modest offense, it signals trouble against a more balanced, explosive unit like Louisville’s.
Pitt’s offense, meanwhile, is pedestrian. The Panthers are 59th in success rate and well outside the top 70 in both third-down conversions and finishing drives. Even if they move the ball between the 20s, putting touchdowns on the board against Louisville’s disciplined defense will be an uphill climb.
The Panthers' quarterback won't help matters either. While Moss has been playing at a relatively high level for his new squad, Eli Holstein picked up right where he left off in 2024 with inconsistent, turnover-plagued football.
He has just a 57 PFF Passing Rating and a Turnover Worthy Play Rate of 7.3%, seventh-worst in the country.
Their 90th ranked Havoc Allowed will start to dip even further if the Cardinals can capitalize here.
Louisville vs Pitt Pick, Betting Analysis
The game hinges on whether Louisville’s offensive line and playmakers can dictate pace. While the Cardinals are just 88th in third-down conversion, their strong early-down success keeps them out of long-yardage situations, where Pitt’s pass rush excels.
Even more telling, Pitt sits 110th in defensive finishing drives. Louisville’s offense thrives on long possessions and red-zone execution, precisely the areas where Pitt struggles most.
Louisville combines offensive consistency, the ability to create explosive plays and a defense that forces inefficient drives. Pittsburgh’s defensive reputation is inflated by weak early opponents and has already cracked against a less efficient West Virginia offense.
Expect Louisville to methodically wear down the Panthers, limit big plays and break the game open late. Louisville is the smart play.
Pick: Louisville -4.5 (Play to -6.5)
