Mehdi Taremi put the Reds ahead in the 6th minute after receiving a long pass from Mohsen Mosalman.
Al Rayyan Brazilian striker Rodrigo Tabata equalized the match in the 19th minute and converted his penalty in the 58th minute.
Persepolis put the Qatari team under pressure but lacked of cutting edge.
With two minutes remaining, Sergio García scored Al Rayyan’s third goal from a set piece.
Earlier in the day, Al Wahda of the UAE drew 2-2 with Saudi Arabia’s Al Hilal at Al Nahyan Stadium.
Al Rayyan move top of the Group D table with six points, followed by Al Hilal and Persepolis with five and four points respectively.