Al Ittihad’s victory saw the club top the group with 15 points, while Sepahan finished five adrift in second place with its Round of 16 hopes hanging in the balance.
Saleh Al Amri scored a sensational free-kick from the right side of the box at King Abdulaziz Stadium for Al Ittihad.
Three minutes after the re-start, Sepahan was level. A long ball into the box from Mohammed Daneshgar found Ramin Rezaeian unmarked at the back post who headed past Al Muaiouf to equalize.
With 20 minutes left to play, goalscorer Al Amri cleverly turned away from his man before he played in Jota, where the Portuguese was able to prod home inside the box for his first AFC Champions League goal.