With under nine minutes remaining in the first half, Blackshear drove past Blue Devils guard Tyus Jones, cut into the lane and exploded for a one-handed jam.
The flush gave the Cardinals a three-point lead.
Over 17 games this season, Blackshear has averaged 12.5 points and 5.3 rebounds.
No. 6 Louisville entered Saturday at 15-2, while No. 4 Duke is 14-2 following consecutive losses to N.C. State and Miami.