Zimbabwean Musawenkosi Mguni scored one and set up the other as Al Shabab capitalised on home advantage to claim only their second win in five games in Group D.
Sepahan, who had Ebrahim Lovinian dismissed in the first half, pulled one back through Emad Mohammed but the Iranian side were unable to find an equaliser as they went crashing out.
Al Shabab were dominant early on, taking the lead after only 65 seconds and creating a number of opportunities to extend their advantage.
Mguni netted with almost his first touch after collecting a superbly weighted ball from Carlos Renato and holding off Hadi Aghily before chipping neatly over the onrushing Rahman Ahmadi.
The goal silenced the vocal travelling support and things could have got worse three minutes later as Renato skipped past two defenders and struck a powerful shot that Ahmadi parried past the post.
Sepahan looked shaken and unsteady as the visitors continued to push forward. Mehrdad Oladi showed great tenacity to ride a tackle and burst down the right wing only to see his fizzing cross cannon off Mguni’s foot and fly over the crossbar.
The Iranians seemed to take encouragement from their fortunate escape and began to muscle their way back into the game.
Their best chance of the first half came on the half-hour mark but Abdulaziz Al Balooshi produced a last-ditch tackle to prevent Emad Mohammed from a certain equaliser.
Eight minutes later, Sepahan’s troubles were compounded when Lovinian, booked moments earlier for a rash late challenge, let out a vicious kick at Essa Shirook and rightly saw red.
The second-half started in similar fashion to the first with Toninho Cerezo’s men looking to exploit the gaps in defence and it didn’t take long until they doubled their advantage through substitute Salem Al Abadla, who was left with a simple tap-in following good work from Mguni.
From then Shabab looked comfortable and should have finished the game, but the home side got complacent, allowing Emad Mohammed to fire a first-time shot past Rabee in the 71st minute.
It looked like the Iranians might have just found a way back into it but Shabab held on for the three points.
