Sepahan should have taken the lead 14 minutes into the match, when Mehdi Karimian macked it against the goalpost from close range after a corner kick.
Just minutes later, Sepahan could thank Rahman Ahmadi for his great save against Mark Bresciano, after the Australian found himself one on one with the Iranian goalkeeper.
The visitors, who had to do without superstar Luca Toni, then broke the deadlock two minutes before the break when Karimian's briliant pass found Bruno Cesar, who excellently lobbed the ball over the keeper.
A controversial scene occured shortly after the restart when Sepahan attempted to give the ball back to Al Nasr after an injury from an Al Nasr player, however, Al Nasr hestitated to pick up the loose ball in the own box and Alabanian striker Xhevahir Sukaj finally decided to do that himself, shortly before being stopped with a foul by Al Nasr's goalkeeper Abdulla Musa Ali.
Ali was sent off and Sepahan awarded a penalty kick, which Omid Ebrahimi deliberately kicked at the goalkeeper in a late act of fairplay.
The game became even more exciting minutes later when Amara Diane was fouled by Ahmadi in the box and a penalty for the homeside was called.
Diane stepped up himself, but Ahmadi brilliantly blocked the spotkick and the striker's following effort from the rebound, before a third attempt went past the post.
Sukaj added a second goal for Sepahan after 67 minutes when he took a powerful run over the left wing following a great throughball from Fabio Januario and sliced the ball into the far corner.
Only moments later, Sukaj almost scored a carbon copy of his goal, but this time aimed inches wide, before substitute midfielder Mehdi Jafarpour also tried his luck a minute afterwards, but his shot went narrowly past the post as well.
Substitute striker Mehdi Seyedsalehi then put the win beyond doubt with his powerful header to a Moharram Navidkia corner after 76 minutes, making it 3-0.
Sepahan top their group after five of six rounds with ten points collected and will host Al Ahli of Saudi Arabia on the final matchday. Al Ahli (7 points) and Lekhwiya of Qatar (6 points) meet later tonight.