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No. 18 Louisville (6-1) will host No. 20 Duke (5-2) in a crucial ACC battle on Saturday afternoon. The Cardinals are coming off their first loss of the season, getting upset by Pittsburgh in a 38-21 final their last time out. They had their bye last week following that upset loss, and they are one of four teams that has one conference loss behind unbeaten Florida State atop the ACC standings. Duke has dropped two of its last three games, including a 38-20 setback at Florida State last week. 

Kickoff is set for 3:30 p.m. ET on Saturday at L&N Federal Credit Union Stadium in Louisville. Louisville is favored by 4.5 points in the latest Louisville vs. Duke odds, while the over/under is set at 46.5 points, per SportsLine consensus. Before entering any Duke vs. Louisville picks, you'll want to see the college football predictions from the model at SportsLine.

The SportsLine Projection Model simulates every FBS college football game 10,000 times. Since its inception, it has generated a stunning profit of well over $2,000 for $100 players on its top-rated college football picks against the spread. Anyone who has followed it has seen huge returns.

The model has set its sights on Duke-Louisville. You can head to SportsLine to see its picks. Here are several college football betting lines for the game:

  • Louisville vs. Duke spread: Louisville -4.5
  • Louisville vs. Duke over/under: 46.5 points
  • Louisville vs. Duke money line: Louisville: -194, Duke: +161
  • Louisville vs. Duke picks: See picks here
  • Louisville vs. Duke live stream: fubo (try for free)

Why Louisville can cover

Louisville had a timely week off following its first loss of the season, which came on the road against Pittsburgh. It was a letdown spot for the Cardinals following a 33-20 win over then-No. 10 Notre Dame the week prior. They have won all three of their home games by double digits, cruising to blowout wins over Murray State and Boston College. 

Duke has completed a total of 12 passes in its last two games combined, as starting quarterback Riley Leonard has been dealing with an injury. He missed a win against NC State before playing three quarters against Florida State last week, and he is questionable for this game. Louisville has covered the spread in eight straight home games, while Duke has won just six of its last 20 games in October. 

Why Duke can cover

If Leonard is forced to miss Saturday's game, the Blue Devils have a strong rushing attack that they can rely on. They are averaging 198.3 rushing yards per game, with veteran running backs Jordan Waters and Jaquez Moore combining for more than 800 rushing yards. Waters, a senior, has rushed for 465 yards and nine touchdowns, averaging 6.0 yards per carry. 

Freshman quarterback Henry Belin IV has gained some valuable experience as a backup over the last two weeks, throwing two touchdown passes in the win over NC State. Louisville is going to be without offensive lineman Renato Brown (knee) for the remainder of the season, while running back Jawhar Jordan (hamstring) is questionable. Duke has covered the spread in eight of its last 11 games, including five of its last six against ACC teams. See which team to pick here. 

How to make Louisville vs. Duke picks

The model has simulated Duke vs. Louisville 10,000 times and the results are in. The model is leaning Over, and it's also generated a point-spread pick that is hitting in more than 60% of simulations. You can only see the pick at SportsLine.

So who wins Louisville vs. Duke, and which side of the spread hits more than 60% of the time? Visit SportsLine now to see which side of the Duke vs. Louisville spread to jump on, all from the advanced computer model that's up well over $2,000 on its top-rated college football spread picks since its inception, and find out.