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.
Al Nassr became the first Saudi team to play in Iran since 2016 and Mohammed Qassem doubled their lead in the 72nd minute 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.
"It was a good game, even though the first half was a little bit difficult for both teams," said Al Nassr forward Sadio Mane.
"We played good in the second half, we created some chances and we scored two goals and I think we deserved to win tonight."
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.
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 were in front by the 11th minute when Laba met Bandar Al Ahbabi's cross from the right at the near post with a deft touch that gave goalkeeper Sanjar Kuvvatov little chance.
He was also involved in the second, benefitting from a mix-up in midfield to gain possession and feed Khalid Al Baloushi, who crisply fired into the corner first time.
With 65 minutes on the clock Laba put the result beyond doubt when he latched onto Park Yong-Woo's pass before steadying himself to spear his shot into the top corner.
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 Feiha.
