Though there are two more votes scheduled, European Commission President, Jean-Claude Juncker, warned that there would be the UK's deal with the EU would be the final one before March 29.
Nicola Sturgeon said the Prime Minister and the government "should be hanging their heads in shame" and demanded that Brexit be delayed and a no-deal outcome ruled out.
Lawmakers voted by 391 to 242 against the deal, the second time they have defeated it.
Brexit skeptics fear a "no-deal" scenario would instantly leave Britain without a whole host of necessary systems to trade and deal with Europe, resulting in food and medicine shortages, airport chaos, immigration crises, and any other number of headaches.
"Finally, the House of Commons is going to have to make a final judgment on what it wants in terms of Brexit", he said.
Markets-sensitive information was set to be released early tomorrow morning on the import tariffs the United Kingdom will impose if it does crash out without a Brexit deal, and on management of the Irish border.
Alan Wager, a Brexit expert at the U.K.in a Changing Europe think tank, said Parliament this week could decisively rule out both May's deal and a no-deal departure.
"The Prime Minister is threatening us all with the danger of No Deal, knowing full well the damage it will do to the British economy", Mr Corbyn said.
"We now have a government that has effectively ceased to function and a country that remains poised on a cliff edge", the First Minister said. While the anti-Brexiteers have continued to say they'll vote "no" and the staunch May supporters have indicated that they'll likely vote "yes", the most pivotal votes will no doubt be the ERG (a group within the Conservatives who represent the Eurosceptic of the party) and the DUP - whose influence amounts to 10 MPs.
"The attorney general has confirmed that there have been no significant changes to the withdrawal agreement despite the legal documents that were agreed last night", Labour Brexit spokesman Keir Starmer said.
And now the statement by the DUP - tweeted by leader Arlene Foster - will be seen as a hammer blow to any lingering hopes that the vote tonight in the House of Commons could go in Mrs May's favour.
Brexit's future is even more uncertain after this latest vote and that could eventually weigh on Wall Street.
"I'm not sure that the agreements with the European Union are a major change...that they continue to be promises of goodwill, but we have heard what the Irish have to say", he said, adding, "Many Conservatives will be heavily influenced by the DUP's (Democratic Unionist Party's) view", which appears to be rejecting the deal.
Mrs May told MPs they would vote tomorrow night on a motion that states: "This House declines to approve leaving the European Union without a Withdrawal Agreement and a Framework on the Future Relationship on 29 March 2019; and notes that leaving without a deal remains the default in United Kingdom and EU law unless this House and the EU ratify an agreement".
"I have got to say that if you look at what the prime minister has said so far it seems to fall short of what she, herself, had promised".
"The smooth functioning of the European Union institutions needs to be ensured".
"We are very clear It is impossible to change our position", Tajani said after he heard about the objections. Many pro-Brexit lawmakers will wait to see that before deciding how to vote. "If there's a solution to the current impasse it can only be found in London".