The move means Cristiano Ronaldo's Al Nassr will kick off their Asian Champions League campaign in Tehran's Azadi Stadium on September 19 against Persepolis while Al Hilal and Al Ittihad will also travel to Iran during the group phase.
Matches had been played on neutral territory since 2016 because strained diplomatic ties between the two countries meant Saudi nationals were not permitted to travel to Iran.
The AFC said it "welcomes the historic move" as it reflects the commitment of Saudi Arabia and Iran "towards fostering closer ties between their respective footballing communities".
It allows "clubs to host matches on their home turf and visiting the respective away stadiums, creating a more engaging and exciting experience for the fans and players alike".
In addition to Al Nassr's visit to Tehran in Group E later this month, Al Hilal, who recently signed Brazil winger Neymar from Paris Saint-Germain, are scheduled to travel to Tehran to take on Nassaji Mazandaran in Group D on October 3.
Saudi Pro League teams have been among the most successful in the Asian club competition, with Al-Hilal winning the title four times while Al Ittihad were champions in 2004 and 2005.
Iran's Persepolis, meanwhile, are one of the region's best supported clubs and played in front of a 100,000 crowd at the Azadi Stadium in the second leg of the 2018 Asian Champions League final, when they lost to Japan's Kashima Antlers.
The group phase kicks off on September 18 and runs to December 13 with the knockout rounds starting on February 12, with the two-legged final scheduled for May 11 and 18.