London's transport authorities stunned the powerful US start-up on Friday when they deemed Uber unfit to run a taxi service for safety reasons and stripped it of its license from September 30, although it can operate while it appeals.
The company said it had 40,000 drivers and 3.5 million customers in London who used its app at least once every three months.
"I know that Uber has become a popular service for many Londoners - but it would be wrong for TfL to license Uber if there was any way this could pose a threat to Londoners' safety or security".
"As such we are lobbying for a stronger national licensing and enforcement approach to this issue".
The TfL decision was backed by the British capital's thousands of black cab drivers.
"A blanket ban will cause massive inconvenience to millions of Londoners, all the while showing that the mayor of London is closed to business and innovation", he said.
Mr Khan said that the regulator had concluded that Uber's conduct meant that it was not fit and proper to hold a private hire licence.
Maria Ludkin, GMB's legal director, said: "As a result of sustained pressure from drivers and the public, Uber has suffered yet another defeat - losing its license to operate in London".
The regulator cited failures to report serious criminal offences, conduct sufficient background checks on drivers and other safety issues, threatening the USA firm's presence in one of the world's wealthiest cities.
"If this decision stands, it will put more than 40,000 licensed drivers out of work and deprive Londoners of a convenient and affordable form of transport", Tom Elvidge, general manager of Uber in London, said in a statement.
Khosrowshahi also pleaded London to work with Uber to "make things right".
A petition set up following the decision has been heavily promoted by Uber.
Uber, which is valued at about US$70 billion (S$95 billion) and whose investors include Goldman Sachs, has faced protests around the world for shaking up long-established taxi markets. Uber drivers use their own cars, and drivers can rent a auto to drive with Uber if they do not own a vehicle.
In an internal email seen by Reuters, Khosrowshahi said there was a "high cost" to having a bad reputation.
Responding to the petition, Fred Jones, Uber's United Kingdom head of cities, told the BBC: "I think people realise that this decision by the mayor and Transport for London is actually because they have caved to pressure from a small number of individuals and groups that want to protect the status quo and reduce consumer choice and competition from London".
The company has some 40,000 drivers on its books, but has been the subject of a fierce campaign against the service by traditional black cab drivers, who say they are subject to much tighter rules and regulations.