Victory came after the hosts had Milad Sarlak sent off for a second bookable offence seven minutes into the second half when the Iranian stepped on Ronaldo's foot during a midfield tussle.
Ten minutes later the former Real Madrid striker released Marcelo Brozovic into the penalty area to unlock the stubborn hosts, with Abdulrahman Ghareeb scoring the opener through a deflected strike from the Croatian's cutback.
Mohammed Qassem doubled Al-Nassr's lead in the 72nd in the Group E encounter as he lashed his shot into the roof of Alireza Beiranvand's net from a tight angle on the left to seal the win.
The game was played in an empty Azadi Stadium as a ban imposed on Persepolis by the Asian Football Confederation two years ago was enforced, depriving thousands of fans who have followed Ronaldo since his arrival in Tehran from attending.
Al-Nassr's win puts them on top of their group, two points ahead of Hernan Crespo-coached Al-Duhail after the Qatari club were held to a 0-0 draw by Tajikistan's FC Istiklol in Dushanbe, also on Tuesday.
In Group A, Al Ain's Togo international Kodjo Laba scored twice and set up his side's third to lead them to a 3-0 win over Uzbekistan's Pakhtakor.
Al Ain are level on three points with Turkmenistan's FC Ahal, who had Elman Tagayew's long-range second-half strike to thank for a surprise 1-0 win over Saudi Arabia's Al Fayha.
Australia's representatives in the competition, Melbourne City, start their campaign on Wednesday night against Japanese side Ventforet Kofu. The second-tier club qualified by winning the Emperor's Cup.
Thai champions Buriram United and China's Zhejiang make up City's group.
