The Hornets collapsed in the third period and then saw all-star forward David West leave the game with a pinched nerve in his back.
Each team has won three games on its home court in the Western Conference semifinal series. Game 7 will be played in New Orleans Monday.
San Antonio owned a seven-point halftime lead, and then took over in the third period when the third and fourth fouls were called on both West and New Orleans guard Chris Paul.
The frustrated Hornets scored just 12 points in the third and fell behind by as many as 24 in the fourth.
Ginobili scored 25 points and Duncan had 20 to go with 15 rebounds. Both sat out most of the fourth period.
Paul paced the Hornets with 21.
West, who made only four of 14 shots from the field and scored 10 points, caught a forearm in the back from Robert Horry and hit the floor early in the fourth quarter. He limped off the court and went directly to the locker room.