Duke Blue Devils vs Louisville Cardinals Pick & Prediction – 1/6/2026

The ACC’s big basketball game on Tuesday night pits the Duke Blue Devils against the Louisville Cardinals at the KFC Yum! Center in Louisville. Both teams have put together strong early-season resumes, but this matchup is a huge litmus test for both of these programs. The winner of this game will determine which team ends the night in first place in the ACC standings. Who will get it done? Continue reading for my Duke vs Louisville prediction.

Our Duke vs Louisville Pick

Game Snapshot

• Matchup: Duke Blue Devils @ Louisville Cardinals
• Date & Time: January 6, 2026, 7:00 PM ET
• Venue: KFC Yum! Center, Louisville, Kentucky
• Broadcast: ESPN

Key Storylines

Duke has established itself as a national title contender with a 13-1 record featuring Quad 1 victories over Michigan State, Florida, Arkansas, and Kansas. The Blue Devils enter Tuesday night ranking high nationally in both offensive and defensive efficiency. Sophomore Cameron Boozer leads the Blue Devils with 23.0 points and 9.8 rebounds per game. Sharpshooter Isaiah Evans just delivered a 28-point effort in Duke’s last outing and his shooting could be a key factor in this game as well.

Louisville hosts this contest with an 11-3 record and has been exceptional at home with an 8-0 record at KFC Yum! Center. Ryan Conwell leads the Cardinals with 19.6 points per game, and Louisville’s offense ranks among the better units in college basketball thanks to prolific three-point shooting and the willingness to push pace. However, Louisville will be without freshman guard Mikel Brown Jr., who averages 16.6 points and 5.1 assists but is out again with a back injury.

Both of these teams rank in the top 10 in the country in offensive efficiency, according to KenPom. They both average over 85 points per game this season and we could be in for an extremely entertaining game because of that. The question will be whether one defense can step up and get some crucial stops against a gifted offensive opponent.

Head-to-Head & Betting Trends

• Duke holds the advantage in this series, winning the last seven meetings and leading the all-time series 17-9.
• Duke is 7-7 against the spread so far this year.
• Louisville has covered the spread 9 times in 14 games so far.
• The under has hit in 9 of Duke’s 14 games.
• The Cardinals are 7-7 in the over/under market heading into Tuesday’s game.

Duke vs Louisville Model Projection

Final Thoughts

Jay Sanin

Jay Sanin is the GM and Head of Sports at ATS.io. He has been writing about sports gambling since 2013, handicapping tens of thousands of sporting events. He plays sides and totals aggressively across most sports and is more selective in player prop markets. He does his own modeling across most sports, and his family is jealous of how much time he spends on his precious spreadsheets.