The battle now is over not whether May loses, but how badly. That would translate into a defeat by a margin of 150 or more, the largest in over a century.
However, the final majority for Tuesday's vote was 230 against, meaning the prime minister has the backing of less than a third of the House of Commons for her flagship deal.
Diplomats are now working on the assumption that exit day will be delayed beyond March 29.
He told MPs that in the event of a Government defeat the agreement would have to return to the Commons later "in much the same form with much the same content". It was defeated by 600 votes to 24.
May's political allies from Northern Ireland, the Democratic Unionist Party, also objected because the backstop treated Northern Ireland differently from other parts of the U.K. The party said that frayed the bond between Northern Ireland and the rest of the country. Former Foreign Secretary Boris Johnson welcomed the imminent demise of the deal and said he would support a no-deal divorce "with zeal and enthusiasm" once it has failed.
First, we now know for certain what had been assumed to be the case for some time: A majority of United Kingdom lawmakers, on all sides of the Brexit divide, so disliked the deal May had cooked up with the European Union that they were willing to kill it.
Leader of the House Andrea Leadsom told the BBC the government was clear that it will not delay or revoke Article 50, although Chancellor Philip Hammond reportedly suggested delaying Brexit in a conference call on Tuesday evening.
Mrs May has proposed a series of meetings with senior parliamentarians and Government representatives over the coming days to break the Brexit deal deadlock.More news: Pregnant duchess laughs after being called 'a fat lady' during charity visit
MPs asked the governor about the bank's stress test scenarios, which included an assessment of a disorderly no-deal Brexit that would trigger an 8% collapse in GDP. And the prime minister's "backstop" solution - temporarily keeping Northern Ireland in the EU customs union as both sides figure out a long-term arrangement - proved to be a key deal-breaker for critics of May's agreement.
The House of Commons will debate the opposition's motion of no confidence, starting after Prime Minister's Questions, shortly after 12.30pm today.
Government whips worked Monday to try to find ways to minimize the scale of the defeat. Last week saw her 11th and 12th defeats. By Tuesday morning, some 30 lawmakers had signed up to that amendment, tabled by the Tory lawmaker Andrew Murrison - including Graham Brady, the influential head of the 1922 Committee of rank-and-file Tories.
Political analyst Anand Menon, from United Kingdom in a Changing Europe, said history is being made week after week in the Brexit saga, with the government being held in contempt even as May soldiers on.
But facing a heavy drubbing, she chose to postpone a parliamentary vote in December on the Brexit deal in the hope of winning concessions from Brussels - and that a Christmas break would change lawmakers' minds. She survived that vote unscathed.
Staring directly at Corbyn, May said that everyone who thought they could go to Brussels and get a better deal was deluding themselves. Some people are confident that if May threatens to walk away, having proved once and for all that her parliament hates the deal, the European Union will blink. Germany denied the report.
Labour politicians reacted to the Leadsom interview with suggestions there is a reluctance to involve their leader Jeremy Corbyn in face-to-face talks with May about a way forward.
The no-confidence vote on May's government is completely different from the no-confidence vote she faced in December, when members of her own Conservative Party challenged her role as party leader. He wanted to avoid voting alongside "those who are there because their strategy is actually to prevent Brexit at all", he told lawmakers.