Louisville Cardinals vs SMU Mustangs, Pick and Prediction, November 22nd, 2025
Two teams in the ACC will go head-to-head when SMU hosts Louisville on Saturday at 12:00 p.m. EST in Gerald J. Ford Stadium. Check out our Louisville Cardinals vs SMU Mustangs pick and prediction here!
Louisville is currently 7th in the conference with a 4-3 conference record and a 7-3 overall record. They are hoping to avoid making it a three-game losing streak with a win on Saturday. Meanwhile, SMU is sitting at fourth in the conference with a 5-1 conference record and a 7-3 overall record. They are on a two-game winning streak and are looking to make it three with a home win. SMU is favored by 2.5 points favorite while the total is set at 52 points. Can Louisville come up with an upset win on the road?
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Cardinals Keep Losing Close Games
Louisville fell by a close margin to Clemson in their latest contest, losing by a score of 20-19. Miller Moss completed 19/27 passes for 212 yards, but Caulin Lucy threw the only touchdown on the day for the Cardinals. Keyjuan Brown had 15 rushes for 135 yards to lead the team and yet Miller Moss had the only rushing touchdown. Chris Bell led the receiving team with five catches for 79 yards, but Nate Kurisky caught the lone TD pass on the day for Louisville. Antonio Watts had four tackles with three assists to lead the defensive unit, but Clev Lubin got the only sack for the Cardinals.
Miller Moss is the primary QB for the Cardinals, and he has completed 64.3% of his passes for 2,344 yards, 11 touchdowns, and seven interceptions. Isaac Brown still leads the team in rushing with 782 yards, while Brown is second with 592 but has the most touchdowns with six. Chris Bell has the most receptions and yards with 67 and 871, respectively. He also has a team-high six TD receptions. On the defensive side, TJ Quinn has the most total tackles with 72, while nobody else has more than 60. Rene Konga and D'Angelo Hutchinson each have five passes defended to lead the squad and Antonio Watts has three interceptions to lead the team. Seven players are listed on the injury report for the Bulldogs, including Brown. All are listed as questionable for Saturday's contest.
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Mustangs Mustering Wins
SMU took care of business last week, defeating Boston College by a score of 45-13. Kevin Jennings completed 16/32 passes for 326 yards, three touchdowns, and one interception. T.J. Harden rushed for a team-high 130 yards on 16 carries, but Derrick McFall was the goal-line back with three TDs on the ground. Three different players caught a TD pass for the Mustangs, but Yamir Knight led all receivers with seven receptions for 162 yards. Jordan Hudson was not far behind with five receptions for 104 yards and a score. Defensively, Isaiah Smith had seven tackles and two tackle assists while also having an impressive four sacks on the day. Tyren Polley caught the lone pick for the Mustangs.
Jennings is the primary QB for the Broncos, completing 64.8% of his passes for 2,810 yards, 21 touchdowns, and nine interceptions. Harden eads the rushing attack with 613 yards and six touchdowns on 133 carries, while nobody else has more than 50 carries and 325 yards. While Hudson has the most receptions and receiving yards with 42 and 595, Romello Brinson is close behind with 40 catches and 582 yards receiving. Knight and Hudson are tied with the most TD receptions with four each. Isaiah Nwokobia has the most total tackles with 77, but Ahmaad Moses is close behind with 73. Nobody else has more than 50, however. Isaiah Smith is the sack leader with eight and three different players each have a team-high seven passes defended. Moses has the most interceptions by far with five while nobody else has more than two. Fourteen players are listed on the injury report, but all are considered questionable to play on Saturday.
Louisville vs SMU Pick
Spread Pick for Louisville vs SMU
- SMU Mustangs -2.5 (4 units)
Aside from having the home crowd advantage behind them, SMU has the momentum with a two-game winning streak vs Louisville's two-game losing streak. SMU will have had an extra week of rest between their previous game and this one, and the Mustangs have won in five of their last six games, covering in four of their last five. The injury to Louisville's top running back in Brown is significant and Louisville has gone 3-7 ATS in their last ten. I trust SMU's offense more to outscore Louisville than the other way around.
Over/Under pick for Louisville vs SMU
- Over 52 (4 units)
The total is a bit higher than what I would have liked to see, but ACC matchups are traditionally high-scoring. SMU has scored an average of over 30 points per game across their last six games and Louisville has scored at least 24 points in all but one of their games this season. I trust Louisville to produce at least 25 points here and SMU should be able to reach 30+ points against a defense that has surrendered around 24 points per game in their last seven. In their only head-to-head meeting in October of 2024, these two teams combined to score 61 points when the total was set at 55.
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