Mehdi Taremi scored the only goal of the match in the 79th just minutes after coming off the bench.
Uruguay dominated the match in the first half but Iran showed a better performance in the second half and won the match.
Carlos Queiroz’s side will play Senegal on September 27.
Team Melli will play one more friendly in November ahead of the 2022 FIFA World Cup but the opponent has not yet been decided.
Iran has been drawn in Group B along with England, the US and Wales.