Theresa May's "hard Brexit" plan could rip the UK apart, Sadiq Khan will claim on Wednesday (18 January).
The Mayor of London will issue the warning to business and political leaders at the 47th World Economic Forum in Davos, Switzerland.
"A hard-line approach to Brexit may hold the Conservative Party together, but it could rip Britain apart," he will say.
"And if we continue on this path – towards a 'hard Brexit' – we risk having to explain to future generations why we knowingly put their economy, their prosperity and their place on the world stage in such peril."
The top Labour figure will call for "privileged access" for London to the EU's single-market after May revealed that she would not seek to maintain the UK's membership of the single-market.
"A 'hard Brexit' would cut Europe off from its only truly global financial centre. This would be bad news for Europe as well as Britain. So a hard Brexit really would be a lose-lose situation," Khan will add.
"Tell your political leaders that a 'hard Brexit' deal is not in the best interests of your company. This won't be easy. But I'm confident that despite the prime minister's rhetoric, there is still a sensible deal to be done."
Khan's speech will come a day before May plans to address the World Economic Forum. The Conservative premier has called for a comprehensive free trade agreement with the EU.
The position would allow the UK to introduce curbs on EU immigration – outlawed under Brussels' free movement of people rules – and enable Whitehall to broker its own free trade deals.
"I do not want Britain to be part of the Common Commercial Policy and I do not want us to be bound by the Common External Tariff," May said.
"These are the elements of the Customs Union that prevent us from striking our own comprehensive trade agreements with other countries. But I do want us to have a customs agreement with the EU.
"Whether that means we must reach a completely new customs agreement, become an associate member of the Customs Union in some way or remain a signatory to some elements of it, I hold no preconceived position.
"I have an open mind on how we do it. It is not the means that matter, but the ends."
The prime minister plans to invoke Article 50 – the mechanism to break from Brussels – and trigger talks with the EU by the end of March.