Pezeshkian received more than 16 million votes against former nuclear negotiator Saeed Jalili with more than 13 million out of over 30 million votes cast, electoral authorities said.
"By gaining majority of the votes cast on Friday, Pezeshkian has become Iran's next president," the interior ministry said.
The runoff on Friday followed a June 28 ballot in a snap election to find a successor to President Ebrahim Raeisi who lost his life with his foreign minister Hossein Amir-Abdollahian and others in a helicopter crash in northwest Iran.
Pezeshkian originally ran against a field of five candidates last week, winning the largest number of votes but falling short of a majority which sent him and Jalili to a second round.
In his first message after the election win, Pezeshkian thanked Iranians who came to vote "with love and to help" the country.
"We will extend the hand of friendship to everyone; we are all people of this country; we should use everyone for the progress of the country," he said on national television.
Electoral authorities put participation in the runoff election at around 50 percent.
A heart surgeon by profession, Pezeshkian entered politics first as the country's deputy health minister and later as the health minister.
In 2006, Pezeshkian was elected as a lawmaker representing Tabriz in northwest Iran. He later served as a deputy parliament speaker described by many as an “independent” politician, a label that was embraced by Pezeshkian in the campaign.