20 Louisville vs SMU NCAAF Pick: Cardinals Seek First Win vs Mustangs (Nov 22)

Published Nov 20, 12:32pm ET by

Gabriel Kozlow - Betting Preview Analyst and Sports Writer

Last updated Nov 20, 12:32pm ET

Pick status
UCF will play Iowa State in the NCAAF on October 19

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Updated Nov 20, 12:32pm ET

  • #20 Louisville (7-3) is coming off a 19-20 loss to Clemson.
  • SMU (7-3) clobbered Boston College with a 45-13 scoreline.
  • Their last matchup was on October 5th, 2024, with SMU winning 34-27.

The Louisville Cardinals are paying a visit to the SMU Mustangs in an ACC battle and their fourth all-time matchup. The Cardinals have never beaten SMU in their historic series (0–3), so they’ll be looking to earn their first-ever win against the Mustangs.

SMU MUSTANGS vs. LOUISVILLE CARDINALS Overview Watch On: ESPN2

DATE & TIME

SATURDAY, NOVEMBER 22, 2025 @ 12:00 PM ET
SMU MUSTANGS
Gerald J. Ford Stadium
Dallas, TX
LOUISVILLE CARDINALS
GAME ODDS
BetOnline
SMU MUSTANGS -135
LOUISVILLE CARDINALS +115

Louisville Seek First-Ever Win Over SMU

Louisville will be heading to Gerald J. Ford Stadium in Dallas this weekend to try and prevent their losing streak from continuing. They are coming off losses to Clemson and California in the past weeks and have basically thrown their season down the drain. The Cardinals enter this game as slight underdogs with a +2.5 point spread.

Chris Bell, their star wide receiver, will be looking to continue his production, having 6 touchdowns from 67 receptions this season. He’ll need his counterpart, QB Miller Moss, to be looking for him on the field and avoid throwing an 8th interception this campaign.

Mustangs Look to Stay in ACC Title Hunt

SMU is riding a two-game winning streak, with victories against Boston College and Miami in overtime. They’ll be looking to continue their unbeaten run versus the Cardinals, extend their overall winning streak, and climb the ACC standings. SMU is currently 5–1 in conference play, making them one of the top teams in the ACC.

Much of SMU’s success is due to QB Kevin Jennings, who already has 21 TDs and 2,810 passing yards. Another high point for the Mustangs is their defensive presence, with DE Isiaiah Smith leading the team with 8 sacks so far this year.

#20 Louisville vs SMU NCAAF Pick

Despite both teams sharing the same 7–3 record, SMU is riding strong momentum, which is why the Mustangs are favored by -2.5. The total is set at 53.5, so we can expect both teams to put points on the board in what should be a tight matchup. The moneyline is -135 for the home team, while the Cardinals are +115.

SMU is playing at home, has better form heading into the game, and has never lost to Louisville. All those factors make us lean toward SMU covering the spread here, so our pick for this game is SMU -2.5.

Pick
SMU -2.5
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