The Iranians had won the first leg of the quarter-final 1-0 at the Foolad Shahr Stadium but were subsequently found to have fielded an ineligible player and Al Sadd were awarded a 3-0 victory instead.
It left Sepahan with a mountain to climb in Doha but first-half goals from Emad Mohammed and Hassan Jafari gave the visitors hope they could pull off a remarkable turnaround.
However, Mamadou Niang's late strike ensured Al Sadd held onto their advantage and they will now face Suwon Samsung Bluewings in the last four.
In a lively start to the contest, Nadir Belhadj saw a close-range shot deflected behind by a Sepahan defender before the visitors stunned the home crowd by taking the lead in the sixth minute when Mohammed unleashed a fierce strike from distance that flew past Al Sadd keeper Mohammed Saqr and into the back of the net.
Saqr denied the same player at full stretch in the 12th minute after the Iraqi striker's shot from the edge of the box before Jafari doubled Sepahan's advantage quarter of an hour later when he collected a loose ball just outside the area and fired past Saqr.
Belhadj weaved his way past two Sepahan defenders just after the half-hour mark but team-mate Abdul Kader Keita was slow to react to his pass with only goalkeeper Reza Mohammadi to beat.
Naseer Nabeel then went close two minutes before the break as Al Sadd pressed for the goal they needed to calm their supporters' nerves.
Wesam Rizik spurned an opportunity in the 58th minute when he won possession from the Sepahan goalkeeper but sliced his finish into the side netting.
Al Sadd coach Jorge Fossati then introduced Hasan Al Haydos for Khalfan Ibrahim in the 66th minute and the substitute made an immediate when he twice fed Keita with superb balls only to see the tall striker fire straight at Mohammadi on both occasions.
Belhadj tested the keeper from outside the area two minutes later and with time running out, Al Sadd eventually killed off Sepahan hopes when Al Haydos fed Niang and he curled a finish past Mohammadi to seal his side's passage into the last four.