British Prime Minister Theresa May’s Brexit deal suffered a crushing defeat in Parliament on Wednesday morning as UK MPs overwhelmingly voted to reject her “breakthrough” agreement to leave the European Union.

With just over two weeks left before Britain is due to leave the EU, the House of Commons voted 391 to 242 to reject Ms May’s long-negotiated and contentious Brexit deal.

Parliament will hold a second vote on Thursday (Australian time) to seek agreement on a no-deal Brexit. If that vote is defeated, a further vote will be held Friday to seek to extend the Brexit deadline.

Speaking after the loss, Ms May said Thursday’s vote would be a conscience vote and she would advise her MPs to reject a no-deal Brexit, citing the “potential damage” of leaving the EU without an agreement.

“This is an issue of grave importance for the future of our country.  Just like the referendum, there are strongly held and equally legitimate views on both sides,” the Prime Minister said.

She said if Parliament ultimately decides to extend the Brexit deadline, MPs must also decide what to do with that extension, including holding a second referendum on the decision to leave.

Opposition Leader Jeremy Corbyn said the government’s second major Brexit defeat should be a trigger for a general election.

Mr Corbyn called for the no-deal Brexit to be taken off the table, saying Ms May had run down the clock on negotiations, “but now the clock has run down on her”.

The EU’s chief Brexit negotiator, Michel Barnier, tweeted that Europe had done everything it could to help get the agreement passed.

The EU has done everything it can to help get the Withdrawal Agreement over the line. The impasse can only be solved in the #UK. Our “no-deal” preparations are now more important than ever before.

— Michel Barnier (@MichelBarnier) March 12, 2019

The Brexit deal appeared doomed to fail before the vote when leading members of her own Conservative Party and Northern Ireland MPs said they would not recommend that members vote for the deal.

The so-called Star Chamber of lawyers convened by the Leave-backing European Research Group found that agreements reached by the Prime Minister in eleventh-hour talks in Strasbourg do not deliver the legally-binding changes the Commons demanded.

Their judgment came after Attorney General Geoffrey Cox told MPs that the changes “reduce the risk” that the UK could be trapped indefinitely in the backstop, but do not remove it altogether.

Ms May, battling a croaky voice and with husband Philip watching from the Commons gallery, warned MPs that “Brexit could be lost” if her deal was rejected again by MPs.

But in a significant setback to Ms May’s effort to overturn the 230-vote majority by which her deal was rejected in January, Mr Cox said “the legal risk remains unchanged” of the UK being unable to leave the backstop without EU agreement.

Shadow Brexit secretary Keir Starmer said Mr Cox had confirmed that “no significant changes” had been secured in two months of negotiations and the government’s strategy was “in tatters”.

Mr Cox’s advice was issued the morning after Ms May’s dash to Strasbourg to finalise a deal with European Commission president Jean-Claude Juncker which she said would reassure MPs that the backstop arrangements to avoid a hard border in Ireland after Brexit will not become permanent.

Mr Cox said newly negotiated deal did not remove the Irish backstop. Photo: Getty

In a statement, the DUP indicated it would not support the deal, saying: “We recognise that the Prime Minister has made limited progress in her discussions with the European Union.”

Their decision was highly influential on many of the Conservatives who rebelled in the first “meaningful vote” because of their concern over the impact of the Withdrawal Agreement on Northern Ireland.

Brexit-backing Tory backbencher Andrea Jenkyns tweeted: “Nothing has really changed, and it is still a bad deal so unable to vote for this.”

Mr Juncker warned that if MPs voted down the deal a second time, “there will be no third chance”. And he said that any extension of the two-year Article 50 negotiation process could not go beyond May 23 unless the UK took part in European Parliament elections beginning that day.

-with AAP