The most optimistic Brexit scenario outlined, of a two-year transition period leading to single market membership without the customs union would still lead to a loss of 176,000 jobs and £20.2 billion in investment.
While the analysis says London's economic output could be as much as 2% lower than predicted under the status quo, it also suggests this would be below a national fall of between 3 per cent and 3.3 per cent lower.
The study said that in a no-deal scenario, the industry that fares the worst would be financial and professional services, with as many as 119,000 fewer jobs nationwide.
"If the government continue to mishandle the negotiations we could be heading for a lost decade of lower growth and lower employment", Khan said.
Labour mayor Khan, who campaigned for Remain, told Sky News: "The analysis concludes that the harder the Brexit we end up with, the bigger the potential impact on jobs, growth and living standards".
Khan commissioned the research after Brexit secretary David Davis said the government had failed to analyse the potential impact of Brexit on specific sectors.
Mr Khan is warning that with just 10 months to go, time is running out.
Conducted by Cambridge Econometrics, the assessment also considers scenarios such as leaving the single market, the customs union - or leaving both.
"And the reason why it's so important is because whatever deal the government negotiates has a direct impact on the quality of lives of families across the country".
London's chief digital officer, Theo Blackwell, said: "London's science and tech sectors are some of the most innovative and exciting parts of our economy and are the rival of anywhere in the world for their dynamism and creativity". While the forward-looking Cambridge study is dealing in potentialities, recruiters on the ground in London question Morgan McKinley's historic figures for December: when it comes to front office recruitment, at least, they say they're far busier than they were previous year.
Khan urged Prime Minister Theresa May to ensure Britain avoids this outcome by negotiating "a deal that enables us to remain in both the single market and the customs union".