The visitors were always facing a difficult task when Mohsen Bengar was sent off in the 16th minute but they took a surprise lead through Rasoul Khatibi on the stroke of half-time.
But second-half strikes from substitutes Abdulrahman Al Qahtani and Al Hamad secured a first win for Al Ettifaq in Group D.
With Al Shabab of the United Arab Emirates downing Uzbek champions Bunyodkor in the other Group D game, all four teams now have three points each.
The hosts started well as Salah Aqqal sent Prince Tagoe through on goal for the hosts in the 13th minute but the Ghanaian striker scuffed his shot into the side netting.
Tagoe then won his side a penalty three minutes later when he chased onto a long ball over the Sepahan defence before tumbling in the area under the attention of Bengar.
Korean referee Kim Dong-jin immediately pointed to the spot before showing Bengar the red card and Bashar stepped up to take the spot kick but Rahman Ahmadi dived to his left to deny the forward.
Chances for either side dried up after that although Tagoe failed to make the most of good break by Al Ettifaq in the 38th minute while Rashed Al Rahab shot high and wide three minutes later.
But the visitors stunned Al Ettifaq when they took the lead with their first shot on target in stoppage time at the end of the half.
Ehsan Haji Safi crossed from the edge of the area and Khatibi rose highest to loop a header over goalkeeper Hussain Shaian and into the back of the net.
Al Ettifaq looked to make a quick response early in the second half and came within inches of equalising when Sayyaf Albishi’s header from a corner grazed the crossbar.
But they drew level in the 63rd minute when Aqqal whipped a cross into the area and though Saleh Bashar missed his attempted volley, the ball found Al Qahtani, who had come on at half-time, and the midfielder struck a low left foot drive into the corner of the net.
Ahmadi saved well from Al Rahab’s angled drive nine minutes later before Tagoe had a goal wiped out for offside a minute later.
The hosts continued to dominate as they looked to grab a winner and Albishi slipped to volley wide when in a good position with eight minutes remaining.
But the winner duly arrived for Al Ettifaq with just four minutes remaining when Al Hamad, who had been on the pitch only a matter of minutes, struck a fine 25-yard effort into the back of the net with Ahmadi stranded.