Abdullah Madu and Abderrazak Hamdallah sealed the points for the Saudi Pro League side in 32nd and 42nd minutes.
The result leaves Al-Nassr at the helm of Group D with 10 points, seven points ahead of third placed Sepahan.
Al-Nassr sealed its place at the Round of 16.
Sepahan faces an uphill battle to catch up with Al-Sadd in second place, who is five points ahead of the team.