The measures include banning travel to and from the cities of Tehran, Karaj, Mashhad, Isfahan and Urmia, Health Ministry official Kianoush Jahanpour told national television.
The travel ban aims to reduce risks ahead of a religious holiday on Saturday, Jahanpour said.
It runs from midnight until Sunday noon, only involving private vehicles but not "public transportation" such as buses and planes, he said.
Under the plan, police will stop vehicles from entering the five cities if their license plates don't match the city they're entering. Many Iranians travel to Mashhad, some 900 kilometers (560 miles) northeast of Tehran, to visit the shrine of Imam Reza (PBUH), Iran’s holiest Shia site.
According to Jahanpour, the measure may be renewed after Sunday and extended to other cities.
The aim was to dissuade Iranians from traveling at the weekend, which runs from Thursday to Friday in Iran, and a public holiday on Saturday.
Deaths and infections from the virus have been on a sharply rising trajectory in Iran since early September.
Iran’s Health Minister Saeed Namaki warned of “very difficult months” ahead in the country.
Coronavirus deaths numbered 279 on Wednesday as 4,830 new cases of infection were confirmed, the highest single-day figures since the Iran reported its first cases in February.
Iran struggles with the worst outbreak in the Middle East, with more than 513,000 confirmed cases. It has seen a total of 29,349 deaths and 414,800 recoveries since February.
The numbers are likely to be higher than officially reported, Deputy Health Minister Iraj Harirchi said Wednesday, primarily due to testing and reporting protocols.
Iran on Saturday started imposing fines for the first time for breaches of health rules in the capital.
Tehran authorities on October 3 shut most public spaces and canceled gatherings for a week, a move that was extended to Wednesday.
To fight rising infections, the government also made face mask-wearing in public places in Tehran mandatory, warning that violators will be fined. Authorities plan to impose the same restrictions in other large cities.
AFP, AP and Reuters contributed to this story.