Getting another vote on a deal would be tricky, as parliament speaker John Bercow has already warned he will not let her bring the same deal back again and again.
The Withdrawal Agreement, which Barnier said "represents a carefully balanced compromise" and took two years to negotiate, "is not open for renegotiation", Barnier reminded the audience.
Some of the MPs who had opposed her plans were swayed after Mrs May said earlier this week that she would quit as prime minister if her deal, agreed with the European Union in November previous year, got through parliament. The Political Declaration is a shorter, 26-page document setting out the UK's aspirations for future relations with the EU.
If the government wins the vote, it believes it will have satisfied the conditions set by the European Union in order to delay Britain's exit from the bloc until May 22.
She now faces having to explain what happens next, after EU Council President Donald Tusk immediately called a Brussels summit for April 10. It will be for the United Kingdom to indicate the way forward before that date, for consideration by the European Council.
"Britain is at a dead end", said Nathalie Loiseau, who was France's Europe minister until she resigned this past week to run in the May 23-26 European Union elections. Get us out on the 12th of April.
France's Emmanuel Macron said on April 12, "we will have to decide on the timeframe to implement (a no-deal exit) ... and therefore we will accelerate the final phase of preparations", Macron said. However our firm preference remains keeping Scotland in the EU.
The commission added that the advantages of the withdrawal agreement will not be replicated in a no-deal exit, including a transition period. "Sectoral mini-deals are not an option".
A proposal for a new customs union got close to passing in a first round, as did a plan for a referendum on May's deal, with more voting planned next Monday and Wednesday. If one of the options receives a majority, the government could use it as a basis for negotiating changes to the political declaration.
The rejection of May's plan raises the chances of further delays to Brexit, or of Britain crashing out of Europe with no deal on the new deadline of April 12.
Retired charity worker Mandy Childs, one of a band of hard-core Brexit supporters who walked across England to London under the slogan "Leave Means Leave", said she felt "heartbroken".
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Her Northern Irish allies, the Democratic Unionist Party (DUP), also continue to insist that its arrangements for the Irish border are unacceptable.
"I will vote for the motion.to achieve two essential outcomes: stave off a longer extension and prevent European elections in May", Raab told Parliament.
Jeremy Corbyn, leader of the Labour Party, again panned the withdrawal deal and after the vote called for May to step aside. "This House has rejected 'no deal.' It has rejected 'no Brexit.' On Wednesday, it rejected all the variations of the deal on the table".
If they don't believe us then they should give us a general election and we will show them in no uncertain terms how much we despise them and how much we now want to drain the swamp.
But Scottish Secretary David Mundell hit back: "SNP and Labour MPs gloat as the PM's deal is voted down".