Oxford Street will be pedestrianised by 2020, the Mayor of London's office has announced.
The central London shopping hub is one of the busiest in the capital and is visited by more than four million people a week, according to The Times.
The plan will be rolled out it two stages to reduce disruption on the 1.2-mile stretch.
Valerie Shawcross, London's deputy mayor for transport, told the London Assembly that the plan was to ban all vehicles from Tottenham Court Road to beyond Selfridges and the entrance to Bond Street Tube station.
The ban will be first implemented on the eastern section, from Oxford Circus onwards, she said.
The plan, reported in The Times, is part of new mayor Sadiq Khan's commitment to tackle air pollution in the city.
He has already pledged to introduce a charge for the most polluting vehicles.
The pedestrianisation will coincide with the opening of Crossrail - a new east-west train line.
Cars are already banned on most of Oxford Street between 7am and 7pm on every day apart from Sunday, but it is a major thoroughfare for buses and taxis.