With just over two months to go until the scheduled Brexit date of March 29, this leaves Britain in limbo and the world on tenterhooks about what will happen next.
MPs from all parties had opposed the agreement for different reasons, according to agency reports.
On the eve of the vote, May had urged them to look again. "No, it is not perfect. And yes, it is a compromise," she said. "But when the history books are written, people will look at the decision of this House... and ask: did we deliver on the country's vote to leave the European Union? Or did we let the British people down?"
On Monday, May had published further assurances from the EU. European Commission President Jean-Claude Juncker and European Council President Donald Tusk repeated in a letter that they would not reopen the divorce deal, but offered clarifications with "legal value" on a controversial clause.
The criticism against the deal has been focused on an arrangement to keep the border with Ireland open by aligning Britain with some EU trade rules, until such time that London and Brussels arrive at a new economic partnership.
Tusk and Juncker said the EU "does not wish to see the backstop enter into force" and noted that if it was necessary, it would only be temporary. They promised to work quickly to find alternatives to keep the border open, including using technology -- a solution backed by Brexit supporters.
The pair repeated that similar assurances to this nature made at an EU summit in December "have legal value". May conceded, however, that the EU had rejected her request for a time limit to the backstop should it come into effect.
After 18 months of gruelling talks, the deal was agreed to between Britain and the EU in November last year. However, hardline Brexit supporters feared that the deal kept Britain too closely tied to the EU and represented a "betrayal". Pro-Europeans, on the other hand, argued that it left the country half-in, half-out.