Prime Minister Theresa May's Brexit deal has been rejected by 230 votes - the largest defeat for a sitting government in history.
MPs voted by 432 votes to 202 to reject the deal, which sets out the terms of Britain's exit from the EU on 29 March.
Labour leader Jeremy Corbyn has now tabled a vote of no confidence in the government, which could trigger a general election.
The confidence vote is expected to be held at about 1900 GMT on Wednesday.
But DUP leader Arlene Foster said her party, which keeps Mrs May in power, would be supporting her in Wednesday's confidence vote.
She told the BBC MPs had "acted in the best interests of the entire United Kingdom" by voting down the deal.
But she added: "We will give the government the space to set out a plan to secure a better deal."
Some 118 Conservative MPs voted with the opposition parties against Mrs May's deal.
Only three Labour MPs supported the prime minister's deal: Ian Austin (Dudley North), Kevin Barron (Rother Valley) and John Mann (Bassetlaw).
In normal times, such a crushing defeat on a key piece of government legislation would be expected to be followed by a prime ministerial resignation.
But Mrs May signalled her intention to carry on in a statement immediately after the vote.
"The House has spoken and this government will listen," she told MPs.
She offered cross-party talks to determine a way forward on Brexit, if she succeeded in winning the confidence vote.
Former foreign secretary and leading Brexiteer Boris Johnson said it was a "bigger defeat than people have been expecting" - and it meant Mrs May's deal was now "dead".
But he said it gave the prime minister a "massive mandate to go back to Brussels" to negotiate a better deal, without the controversial Northern Ireland backstop.
And he said he would back Mrs May in Wednesday's confidence vote.
Labour MP Chuka Umunna said that if his leader did not secure a general election, Mr Corbyn should do what the "overwhelming majority" of Labour members want and get behind a further EU referendum.
Lib Dem leader Sir Vince Cable, who also wants a second referendum, said Mrs May's defeat was "the beginning of the end of Brexit" - but conceded that campaigners would not get one without Mr Corbyn's backing.
Scotland's First Minister Nicola Sturgeon said Mrs May had suffered "a defeat of historic proportions" and called again for the Article 50 "clock to be stopped" in order for another referendum to take place.
"We have reached the point now where it would be unconscionable to kick the can any further down the road," she said.
However, government minister Rory Stewart said there was no majority in the Commons for any Brexit plan, including another referendum.
How a confidence motion works
By the BBC's head of political research Peter Barnes
Under the Fixed Term Parliaments Act 2011, UK general elections are only supposed to happen every five years. The next one is due in 2022.
But a vote of no confidence lets MPs decide on whether they want the government to continue. The motion must be worded: "That this House has no confidence in Her Majesty's Government."
If a majority of MPs vote for the motion then it starts a 14-day countdown.
If during that time the current government, or any other alternative government cannot win a new vote of confidence, then an early general election would be called.
That election cannot happen for at least 25 working days.
In her statement to MPs, Mrs May said she planned to return to the Commons next Monday with an alternative plan - if she survives the confidence vote.
She said she would explore any ideas from cross-party talks with the EU, but she remained committed to delivering on the result of the 2016 referendum.
President of the European Council, Donald Tusk, said he regretted the outcome of the vote and urged the UK government to "clarify its intentions with respect to its next steps as soon as possible".