The day after her parliamentary loss by the worst margin for a British government in modern times, May was widely expected to hold on to power through a confidence vote, having secured the backing of her own party's rebels and its Northern Irish allies.
The confidence motion, called by opposition Labour Party leader Jeremy Corbyn after lawmakers rejected May's Brexit deal by 432-202, will be held at 1900 GMT.
With the clock ticking down to March 29, the date set in law for Brexit, the United Kingdom is now in the deepest political crisis in half a century as it grapples with how, or even whether, to exit the European project it joined in 1973.
After lawmakers in the 800-year-old parliament dismissed May's deal, she pledged to speak to senior parliamentarians to find a compromise that would avoid a disorderly no-deal Brexit or another referendum on membership.
"The prime minister, having got through today, assuming that she does, will then be seeking to talk to senior parliamentarians," House of Commons leader Andrea Leadsom said.
May, an initial opponent of Brexit who won the top job in the political turmoil that followed the referendum vote, will speak to the opposition Labour party, the Northern Irish DUP and her own lawmakers.
Labour's finance minister-in-waiting, John McDonnell, said May could eventually get a deal through parliament if she negotiated a compromise with his party.
Labour says its aim is to win power and negotiate Brexit on better terms. However, many Labour members want to see another referendum with an option to cancel Brexit, and the party says it is ruling out nothing if it fails to bring May down.
May's humiliating loss appears to catastrophically undermine her two-year strategy of forging an amicable divorce with close ties to the EU after the March 29 exit.
The last time an international treaty was defeated by the British parliament was in 1864, when an extradition treaty with Prussia was voted down, according to the Hansard Society.
Sterling jumped by more than a cent against the U.S. dollar on news of May's defeat on Tuesday and was holding close to that level on Wednesday. Despite the failure of May's deal, many investors see the prospect of exiting with no deal at all receding as parliament hardens its stance against it.
May says cancelling Brexit is likelier than leaving with no deal, but she has repeatedly stressed her determination to leave and described any failure to carry out the mandate of the 2016 referendum as "catastrophic" for democracy.
Ever since Britain voted by 52-48 percent to leave the EU in a referendum in June 2016, the political class has been debating how to leave the European project forged by France and Germany after the devastation of World War Two.
As the politicians discussed Brexit, companies were bracing for the possible chaos of a no-deal Brexit that would see trade with the EU switch to World Trade Organization rules. Many companies say this could disrupt supply chains built to rely on friction-free trade. UBS Wealth Management told investors to limit their exposure to UK assets.
Other members of the EU, which combined has about six times the economic might of the United Kingdom, called for discussion but indicated there was little chance of fundamental change to the deal May had negotiated. Germany's Foreign Minister Heiko Maas said there was not much time left to find a Brexit solution and that "the time for playing games is now over".
EU Commission President Jean-Claude Juncker said a disorderly Brexit was more likely while Donald Tusk, the chairman of EU leaders, suggested Britain should now consider reversing Brexit altogether.
Brexit campaigner Nigel Farage said Britain was probably heading for a delay and a another vote on EU membership.
"I think and I fear that we are headed on a path towards delay and probably, yes, a second vote," Farage said.
For the EU, already reeling from successive crises over debt and refugees, Brexit is possibly the biggest blow yet in its 60-year history, though its 27 other members have shown remarkable unity over Britain's exit.
While some EU leaders and many British lawmakers have suggested that Britain might want to change its mind, Britain's leaders are concerned that to stop Brexit could alienate the 17.4 million people who voted to leave.
Brexiteers anticipate some short-term economic pain but say Britain will then thrive if cut loose from what they cast as a doomed experiment in German-dominated unity. Opponents of Brexit say it is folly that will weaken the West, make Britain poorer and torpedo what remains of its post-imperial clout.
(Writing by Guy Faulconbridge; Editing by Andrew Cawthorne and Peter Graff)