It will be Iran's fifth appearance at soccer's premier tournament, reports Xinhua news agency.
Sardar Azmoun scored in the 23rd minute and Mehdi Taremi added the second goal in the 88th minute at the Azadi Stadium here on Monday night.
The win means Iran -- coached by former Real Madrid and Portugal manager Carlos Queiroz -- will finish among the top two places in Group A of Asia's final round of qualifying.
Uzbekistan are eight points behind top-placed Iran at the third spot and have only two games remaining.
The top two teams in each of Asia's two qualifying groups advance automatically to the finals while the teams in third place go through a series of play-offs.
South Korea are in second place in Group A, a point ahead of Uzbekistan with a game in hand.
Brazil were the first team to qualify for next year's World Cup to be held in Russia.