Mrs May is facing mounting pressure from her own party to resign or be ousted, but she insisted today: “I believe in what I’m doing.”
Cabinet ministers joined the revolt, signalling they were no longer willing to back PM after she buckled under pressure and opened the door to a second Brexit referendum.
Leading the charge was Mrs Leadsom, who quit the government at around 7.30 pm.
In her resignation letter, Mrs Leadsom said: “I do not believe that we will be a truly sovereign United Kingdom through the deal that is now proposed. I have always maintained that a second referendum would be dangerously divisive.”
It is with great regret and a heavy heart that I have decided to resign from the Government. pic.twitter.com/f2SOXkaqmH— Andrea Leadsom MP (@andrealeadsom) 22 May 2019
A Number 10 spokesperson said: "We are disappointed that she has chosen to resign, and the prime minister remains focused on delivering the Brexit people voted for."
Other cabinet ministers requested private meetings with the PM to express their fury and demand she change tack or accept she no longer has a hold on power.
Tory backbenchers stepped up their attacks over the course of the day, making their opposition to Mrs May’s leadership clear.
However, the 1922 Committee - a group a powerful backbench MPs - decided no to change the rules of the Tory party to allow MPs another vote on Theresa May’s leadership.
As it stands, a leadership challenge cannot be brought until December as the PM survived a no-confidence vote at the end of last year.
The PM will meet the 1922 Committee on Friday, suggesting her job is safe until then.
And in a highly visible sign that Mrs May’s authority is slipping away, Brexit-supporting colleagues were absent for the start of Prime Minister’s Questions, with Cabinet ministers including Mrs Leadsom only appearing once the session was well under way.
A disastrous performance in the European elections could also precipitate her resignation on Monday.
The Conservative Party is careering towards a humiliation in the European Parliamentary elections.
The gloomiest polls for the Tories predict the party will win just 7% of the vote, behind the Greens and Lib Dems and trailing far behind the Brexit Party who are comfortably in the lead.
It all follows the PM’s last-ditch effort to unite MPs behind her deal yesterday, offering the possibility of a second referendum in an attempt to get Labour behind her.
However her attempt was roundly rejected by a cross-section of Parliament, prompting Tory MPs to abandon her.
Eurosceptics including Boris Johnson and Jacob Rees-Mogg, who have reluctantly backed Mrs May’s Brexit deal in the past, were among those who withdrew their support.
The Withdrawal Agreement Bill (WAB) is scheduled to be published on Friday and MPs are currently set to have a vote in the first week of June, the Government confirmed today.
Defending her Brexit deal in the Commons, Mrs May said voting against the WAB would bring about ‘division and deadlock’.
She said: “We risk leaving with no deal, something this House is clearly against.
We risk stopping Brexit altogether, something the British people would simply not tolerate.
We risk creating further division at a time when we need to be acting together in the national interest.
And we guarantee a future in which our politics become still more polarised and voters increasingly despair as they see us failing to do what they asked of us.
None of us want to see that happen.”