The UK faces a "muddled Brexit" unless Theresa May changes her direction, Sadiq Khan warned on Thursday night (12 January).
The Mayor of London, who campaigned for Remain at the EU referendum, said it was "deeply concerning" that the government seemed confused.
"It's deeply concerning that we still appear to have 'muddled thinking' at the heart of government so soon before the negotiations are set to start," he told City leaders, the Press Association reported.
"For months now, I've been arguing against a hard Brexit. But the only thing that would be as damaging as a hard Brexit is a muddled Brexit."
The speech at Mansion House, London, comes just days before May is to deliver a major address on the issue on 17 January.
The Conservative premier has hinted that the UK will no longer have full access to the EU's single-market as the government seeks immigration curbs.
May, in speech to the Charity Commission on 9 January, said her ministers have a "comprehensive, wide-ranging plan" to split from the EU.
"A plan to build a country where wealth and opportunity are shared; where all of us, no matter what our background, play by the same rules; and where future generations enjoy the same opportunities from which their parents have benefited throughout their lives," she said.
Khan has been holding monthly meetings with Brexit Secretary David Davis. A top concern for the Mayor of London and businesses in the UK capital is passporting and equivalency in regulations once Britian splits with the EU.
Miles Celic, chief executive of the TheCityUK, said: "The industry has been working closely with the government to help identify key priorities for the negotiations.
"We have been clear to stress these should include interim arrangements, access to global talent and expertise, and a bespoke deal based on mutual recognition and regulatory cooperation.
"Ultimately, the best Brexit deal will be one that reduces uncertainty and enables businesses to continue to best serve customers and clients."
Negotiations between the UK and EU will start once May invokes Article 50, the mechanism to split from Brussels, which the prime minister had promised to trigger by the end of March.
The government is also waiting on the Supreme Court's final judgement over whether MPs should vote on the issue. The ruling is expected in January.