Businesses in London's West End need "urgent support" from the government to survive the pandemic, Sadiq Khan says.
In a letter to the prime minister, the Labour mayor said the area was the "UK's economic and cultural powerhouse" employing one in 10 Londoners.
Footfall in the West End is currently 63% lower compared to this time last year, according to figures from the New West End Company.
The government has been approached for comment.
The number of people visiting the the West End increased when non-essential retail stores reopened on 15 June, but the New West End Company said there had been a plateau "at less than half of usual levels" since then.
The group, which represents 600 retailers and landlords in Oxford Street, Bond Street, Regent Street and Mayfair, has forecast a £5bn drop in annual retail sales for businesses in the area.
It has also warned that a third of the 150,000 employees it represents could face redundancy.
Chief Executive Jace Tyrrell described the "next couple of months" as "a defining moment for hundreds of West End businesses" with research showing that people's concern about using public transport was particularly affecting the number of visitors.
Emilio Malik, who runs Mayfair-based Lebanese restaurant Lafeez Tapas, told the BBC putting up the congestion charge and extending its hours was also not helping the situation.
"We're about 75% down [compared to last year]. It's tough. We've been on the street about 15 years now. We've built up a good trade but it's challenging," he said.
In Mr Khan's letter to Boris Johnson, he set out eight proposals which he said would ensure the West End could survive, including extending the business rates holiday beyond the end of March next year and creating a financial aid scheme for London's businesses.
Commenting on the letter, the mayor said London had been the "economic engine of the UK" for decades, with the city accounting for a quarter of the UK's total economic output.
"In the face of a perfect economic storm, our businesses need urgent and sustained support from government to ensure they can survive," he added.
- 10 August