Opposition leader Jeremy Corbyn immediately called for a no-confidence vote, saying Parliament deserved a chance to give its verdict "on the sheer incompetence" of May's government.
Despite not commanding a majority in Parliament, it appeared that May would survive Wednesday's vote because the Democratic Unionist Party — a small Northern Irish group of lawmakers that props up the government — said it would support her.
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If May loses the no-confidence vote, the government will fall. All political parties would have a 14-day period to form a new government in the 650-seat Parliament. If that fails, a general election would be called — which is Corbyn's preference.
Before this week, the biggest government loss in Parliament was by 166 votes in 1926. May smashed that record, losing by 230 votes.
.@theresa_may loses vote on her deal by 202 to 432. Massive humiliation for the prime minister. In normal times, that would be curtains for a PM. These are not normal times.
Tuesday's defeat on Brexit came just 73 days before Britain's scheduled departure from the E.U. on March 29 and throws up a big question mark over what’s next for the country.
If May survives the no-confidence vote, she will return to Parliament next week with an alternative plan to leave the E.U.
But the prime minister has given little indication of what shape her next proposal might take. She will either have to attempt to renegotiate the deal with Brussels or the U.K. will face a "no-deal" scenario that would see Britain crash out of the bloc without a trade agreement, something most experts say would have a catastrophic consequences.
The border is currently more or less invisible and there are no checkpoints. Some fear the reinstatement of a physical boundary risks a return to "The Troubles," rekindling tensions that might spill over into violence. A 1998 peace deal ended decades of conflict.
Leading Brexit campaigner Nigel Farage told broadcaster Sky News on Wednesday that he thought Britain would likely be forced to delay the scheduled date for Brexit and that another referendum on the issue might be necessary to break the government gridlock.
"I think and I fear that we are headed on a path towards delay and probably, yes, a second vote," said Farage, who is a former leader of the pro-Brexit U.K. Independence Party.
Saphora Smith is a London-based reporter for NBC News Digital.