The defeat was widely expected, but the scale of the House of Commons’ vote – 432 votes against the government and 202 in support – was devastating for Ms May’s fragile leadership.
Labour leader Jeremy Corbyn put forward a confidence motion in the aftermath of the crushing loss, which made history as the biggest ever government defeat on the floor of the House of Commons.
The defeat by 230 votes easily beat the previous record of 166 votes, set in 1924 by the minority Labour government of Ramsay MacDonald.
Parliament finally delivered its verdict on the prime minister’s withdrawal agreement after months of debate, as crowds of both Leave and Remain protesters gathered outside parliament to express their anger.
Ms May insisted she intended to stay on, setting out plans for talks with senior parliamentarians in the hope of finding “genuinely negotiable” solutions which she can take to Brussels.
But she faces another crucial vote on Wednesday after the Labour leader moved to table a formal motion of no confidence in her government.
Senior ministers reportedly told top business leaders that a motion to delay the Article 50 process of leaving the EU is being prepared in a conference call following the vote defeat.
To follow events as they unfolded, see our live coverage below:
Welcome to The Independent's coverage of all the news from Westminster on the day of the meaningful vote in Theresa May's Brexit deal.
The Brexit debate will recommence at 1245 today and the votes are expected at 1900.
The voting is likely to last at least two hours as MPs issue their verdict on a number of amendments before finally deciding whether to back Theresa May's Brexit deal.
The speaker John Bercow will reveal which amendments he has selected for a vote as the final day of debate. It is also possible that MPs could decide to drop their amendments and new ones may emerge.
So what are the notable amendments tabled so far?
- Amendment A: Labour's bid to reject Mrs May's deal and "pursue every option" to prevent the UK leaving the EU with no deal. The Liberal Democrats have tabled an amendment to this proposal, which seeks to include a second referendum as one of the options.
- Amendment K: The SNP wants to reject the Brexit deal. It also calls on the UK Government to "respect the will" of the Scottish Parliament and Welsh Assembly in rejecting the Brexit deal.
- Amendment O: Former minister Sir Hugo Swire, along with fellow Tories, wants to ensure parliamentary approval on either extending the transition period or triggering the backstop - should a trade deal not be concluded by the end of 2020. It also aims to push the UK Government to secure further assurances from the EU to limit the backstop to 12 months.
- Amendment P: A Labour backbench amendment to bolster workers' rights and environmental standards.
↵Hilary Benn, Labour chairman of the exiting the European Union committee, has withdrawn his amendment which called for the rejection of Ms May's Brexit deal and intended to prevent a no-deal Brexit.
Mr Benn said he would vote against the motion and intends to pursue a 'no to no deal' vote at the earliest opportunity.
He said that since he had originally tabled his amendment in December, MPs had voted for a no deal amendment to the Finance Bill "which is a clear and very welcome indication of MPs' opposition to no deal".
Mr Benn added that Dominic Grieve's amendment and the Speaker's ruling that a business motion can be amended "are also very important and there is now a proposal for a Bill that would allow the Commons in effect to rule out a no deal Brexit by seeking an extension to Article 50 if necessary".
"All these developments mean that the House will soon have the opportunity to make it clear that it rejects no deal and so offer reassurance to the many businesses and their workers who are very anxious about the disaster that a no deal Brexit would represent.
"If the Prime Minister loses tonight the Government must reach out across the House to try and find a way forward. If this doesn't happen, then Parliament will have to take the lead."
Liberal Democrat leader Sir Vince Cable said the "crushing" verdict of the Lords on the withdrawal agreement will be repeated when MPs vote on the deal.
"Theresa May can only be facing the same crushing defeat in the Commons tonight. She has no Plan B. We do. Time for a Peoples Vote," he tweeted.
Former Tory minister Sam Gyima has tweeted a video explaining why he won't be backing Ms May's deal
Dominic Raab said that Brexiteers like him could back a deal if aspects such as the backstop were dealt with.
The former Brexit secretary, who quit the post in November, said the EU had played "a smart game of hard ball" and said it was time for the UK to do the same, he told BBC Radio 4's Today.
I made clear when I resigned that there were three aspects that needed to be addressed.
The backstop is clearly one of them and I want to see very clearly the Withdrawal Agreement linked to a best-in-class free trade agreement.
If we could do those two things, someone like me would say that actually we could vote for it.
Mr Raab added that payments of the £39 billion "divorce bill" should be negotiated or paid in tranches to the EU in exchange for a free trade deal, saying it was "common sense".
He added: "What I don't think should happen is the EU, through this intransigent stubbornness and, to some degree, bullying, should stop us leaving in March 2019, and that is crucial."
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