Amile Jefferson added 19 points to help Duke hand Louisville its first double-digit loss in 3 years. Okafor and Jefferson helped Duke down low, where they outscored the Cardinals 33-24 in the paint.
Both teams now sit at 3-2 in conference play in the ACC.
Louisville struggled from the field, shooting just 18 of 61, which is good for 30 percent. It is the second loss in the past week for the Cardinals, who fell to North Carolina last Saturday.
The win puts Duke head coach Mike Krzyzewski 2 wins away from 1,000. Okafor, Jefferson, and Justice Winslow each grabbed 7 rebounds in the victory.
Terry Rozier had 17 points to lead the Cardinals in a losing effort. Louisville trailed for just about the entire game, including falling behind by as many as 21 in the second half. A 15-6 run for Duke gave them a 10-point cushion at the half.
The Cardinals could not stop the Duke run in the first half, despite holding Okafor to just 4 points before the break. Okafor got red hot, scoring 8 of Duke's first 16 points in the second half. The Blue Devils finished the game shooting 49 percent from the floor.
Coach K looks to inch closer to win number 1,000 when he leads his 15-2 Duke team to host Pittsburgh tomorrow night. The Cardinals fall to 15-3 on the season and will visit Pittsburgh next Sunday.