Questions about future trade and regulatory arrangements with the European Union and bitter disagreements over a provision dealing with the border between Ireland and Northern Ireland helped sink the deal, though some critics seem to be opposed to any deal and instead want Brexit to be put up for another vote.
British Prime Minister Theresa May has three sitting days to return to parliament with a "Plan B". She was also quick to point out that the vote made no efforts to put any new plans in place and has no path ahead of it.
Following her humiliation in the Commons last night, Mrs May said she would discuss her deal with "senior" MPs on the Opposition benches to find a way forward. The no-confidence measure, also known as a censure motion, will test whether a majority of lawmakers support the proposition "that this House has no confidence in Her Majesty's Government".
John McDonnell insisted today Labour will keep trying to force a general election if its no confidence motion fails tonight and could swerve backing a second referendum for "weeks".
According to Macron, there's also a third option that the United Kingdom is likely to opt for after attempting to renegotiate the deal. If the party doesn't shift its position, pro-EU lawmakers are planning to propose their own amendment to the next Brexit vote. The substance of the deal negotiated by Prime Minister Theresa May's cabinet with the European Union is "non-negotiable", but some minor details may yet be changed, he suggested. "It would be better for her to realise the error of her ways and adopt a different, more inclusive approach within - and without - the Conservative party".
The result of the vote gave May a massive mandate to go back to Brussels and renegotiate a new deal, said Boris Johnson, former British foreign secretary and ex-Mayor of London.
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"Preparations for all scenarios will continue and be intensified, including the inauspicious scenario of a withdrawal without a deal on March 29", said Italian Prime Minister Giuseppe Conte.
May's government is likewise split.
Over the past week, backbench MPs have worked across the aisle to pass amendments that tied May's hands in the event of her deal being rejected.
In a conference call with business leaders late on Tuesday, chancellor of the Exchequer Philip Hammond floated the idea of delaying Britain's departure from the EU. "The stakes could hardly be higher".
To avoid a chaotic no-deal Brexit, Parliament will need to pass new legislation and to request an extension from the 27 other European Union members that gives breathing space for British lawmakers.
"Crushing defeat", "humiliation", "historic defeat" figured in headlines, while some tabloids sounded a sober note: "Time to put your country first" (Daily Mail), "Don't lose our trust forever" (Daily Express) and 'History will ask...did we deliver Brexit?' (Metro).
"The EU doesn't negotiate with Parliament", he says, "they negotiate with the government".