Lawmakers now have two starkly different choices: no deal or delay.
A look at what might happen in the days ahead:
The House of Commons voted 391-242 against May's EU withdrawal agreement Tuesday, snubbing changes she secured from the bloc the night before to allay concerns about the deal's Irish border provisions. Lawmakers voted down the deal in January by an even bigger margin.
After the tally, May said Parliament would vote Wednesday on whether to abandon efforts to secure an agreement and to leave the EU as planned in a little more than two weeks without a deal.
A phalanx of pro-Brexit politicians supports that idea. They argue it would free the U.K. from EU rules and red tape, allowing the country to forge an independent global trade policy.
But economists and businesses fear a so-called "no-deal Brexit" would hammer the economy as tariffs and other trade barriers go up between Britain and the EU, its biggest trading partner.
In the short term, there could be gridlock at British ports and shortages of fresh produce. In the long run, the government says a no-deal scenario would leave the economy 6 percent to 9 percent smaller over 15 years than remaining in the EU.
Last month, Parliament passed a non-binding amendment ruling out a "no-deal" Brexit, and it is unlikely they will support it now. May said lawmakers would be free to follow their consciences rather than party lines when they consider the question Wednesday.
DELAY, DELAY, DELAY
If lawmakers give leaving the EU without an agreement a thumbs down, they have one choice left: seeking more time. A third vote scheduled for Thursday is on asking the EU to delay Brexit day by up to three months.
This option is likely to prove popular, since politicians on both sides of the Brexit debate fear time is running out to secure an orderly withdrawal by March 29.
Extending the timeframe for Brexit would require approval from all 27 remaining EU member countries. They have an opportunity to grand such a request at a March 21-22 summit in Brussels. But the rest of the EU is reluctant to postpone Brexit beyond the late May elections for the EU's legislature, the European Parliament.
The EU said Tuesday that Britain needs to provide "a credible justification" for any delay.
Whatever Parliament decides, it will not end Britain's Brexit crisis. Both lawmakers and the public remain split between backers of a clean break from the EU and those who favor continuing a close relationship through a post-Brexit trade deal or by reversing the June 2016 decision to leave.
May is unwilling to abandon her hard-won Brexit agreement and might try to put it to Parliament a third time, although the latest margin of defeat makes that tricky.
Some lawmakers want her to have Parliament consider different forms of Brexit to see if there is a majority for any course of action.
Some think the only way forward is a snap election that could rearrange the forces in Parliament and break the political deadlock. May has ruled that out, but could come to see it as her only option.
And anti-Brexit campaigners haven't abandoned efforts to secure a new referendum on whether to remain in the EU. The government opposes the idea, which at the moment also lacks majority support in Parliament.
However, the political calculus could change if the paralysis drags on. The opposition Labour Party has said it would support a second referendum if other options were exhausted.
It all means more twists are coming in the Brexit drama.
"No one really believes this is the last chance saloon," said Oliver Patel, a research associate at the European Institute at University College London.
Follow AP's full coverage of Brexit at: https://www.apnews.com/Brexit