Senin Sebai scored on the break to put the club from Dushanbe in front with a minute left in the first half and Istiklol held out under relentless pressure until Ronaldo levelled with a clever clipped finish in the 66th minute.
The streets were crowded with fans who raised welcome banners and pictures of Ronaldo upon the arrival of the Saudi Arabian team in Iran after the restoration of relations between the two countries
Roberto Martinez's side have now won all six of their qualifying games, without conceding a single goal and scoring 24 themselves, with this the country's largest ever victory.
"If you love Cristiano Ronaldo, you don’t have to hate (Lionel) Messi. We have both changed the history of world football,” Ronaldo said during an interview during with Record, a Portuguese newspaper.
"I want more," the forward told a press conference before training with the national side at Oeiras, on the outskirts of Lisbon, ahead of upcoming European Championship qualifiers.
Ronaldo scored his sixth goal in his last three games and claimed two assists as Al Nassr recorded a third straight league victory. Sadio Mane was also on the scoresheet.
The Portuguese superstar got things underway in the 13th minute as he converted from the spot after a handball in the Al Shabab penalty area. He added to his tally five minutes later with a header only for the goal to be disallowed for a push on a defender.
This summer's transfer fees alone top $830 million, without counting the players' eye-watering wages, or Ronaldo's January signing in a deal which is said to net him 400 million euros over two-and-a-half years
The Saudi Pro League side came from behind to triumph 4-2 in the play-off at Mrsool Park, with Brazilian Anderson Talisca scoring twice and Croatia international Marcelo Brozovic rounding off the win. Nassr had been two minutes from exiting the tournament