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There's only one FBS matchup on the Thursday college football schedule and it comes in the ACC. The Louisville Cardinals (5-5) travel to Durham, N.C., to take on the Duke Blue Devils (3-7). Louisville's offense caught fire in a 41-3 win over Syracuse last time out, putting the Cardinals one win away from bowl eligibility. The wheels have fallen off for David Cutcliffe's side as the Blue Devils limp into this matchup with six straight losses and just one cover during that span. Duke could be without quarterback Gunnar Holmberg, who is questionable (ribs) for this one, but with a three-score spread to work with, the Blue Devils might be worth backing.

Kickoff at Wallace Wade Stadium is set for 7:30 p.m. ET. Caesars Sportsbook lists the Cardinals as 20-point favorites in the latest Louisville vs. Duke odds. The over-under, or total number of points expected, is set at 60.5. Before locking in any Duke vs. Louisville picks, be sure to see the college football predictions and betting advice from SportsLine's proven computer model.

The model simulates every FBS college football game 10,000 times. Over the past five-plus years, the proprietary computer model has generated a stunning profit of almost $3,500 for $100 players on its top-rated college football picks against the spread. It also enters Week 12 of the 2021 season on a 36-23 run on all top-rated college football side picks. Anyone who has followed it has seen huge returns.

Now, the model has set its sights on Louisville vs. Duke and locked in its picks and predictions. You can visit SportsLine now to see the model's picks. Here are the college football odds and betting lines for Duke vs. Louisville:

  • Louisville vs. Duke spread: Louisville -20
  • Louisville vs. Duke over-under: 60.5 points 
  • Louisville vs. Duke money line: Louisville -1400, Duke +800 
  • LOU: The total has gone under in four of Louisville's last five games 
  • DUKE: The Blue Devils are 4-1 ATS in their previous five home games

Why Louisville can cover

The Cardinals are a respectable 2-2 ATS away from home in 2021. They've won two games by at least 20 points and have momentum on their side after blowing Syracuse out. Dual-threat quarterback Malik Cunningham has been essential to Louisville's success all season. Duke's abysmal defense should have a tough time slowing him down.

Only Arkansas State gave up more points (368) than Duke ahead of Week 12. The Blue Devils struggle to get stops and allow almost 500 total yards per contest. Cunningham is one of the FBS's most electric dual-threat quarterbacks and is responsible for 29 touchdowns this year. Duke's average margin of defeat over the last four weeks is 35.5 points. If the Blue Devils can't limit the Cardinals' signal-caller, the visitors could pull away early. 

Why Duke can cover

Duke has been competitive at home this year. The Blue Devils are 3-2 straight up, and 3-1 ATS as hosts, and they could thrive against a Louisville side that's hasn't blown opposing teams away on the road. The Cardinals are 1-2 straight up on the road, and Florida State is the only ACC team they've beaten away from home. The ground game could be critical to Duke covering against a superior team in this matchup.

Mataeo Durant has 1,095 rushing yards, and nine rushing scores on 220 carries in 2021. The Duke running back has racked up more than 100 all-purpose yards in four of his five home appearances. Louisville is giving up 133 rushing yards per game to opposing teams, so Durant has a chance to put together another productive performance. The home team can cover if he moves the chains consistently and limits the Cardinals' possessions.

How to make Louisville vs. Duke picks

SportsLine's model is leaning under on the total, projecting 59 combined points. It also has generated an against-the-spread pick that cashes in almost 60 percent of simulations. You can only get the model's Duke vs. Louisville picks at SportsLine.

So who wins Louisville vs. Duke? And which side of the spread hits almost 60 percent of the time? Visit SportsLine now to see which side of the spread to back, all from the advanced model that has crushed its college football picks, and find out.