Jo Johnson today threatened to shatter Theresa May's delicate efforts to strike a Brexit deal as he dramatically quit and demanded a fresh referendum.
The Orpington MP, brother of Boris Johnson, said that the emerging package - which the PM hopes to finalise within days - was a massive failure in British statecraft on the scale of Suez.
He said the 'reality' of what was being negotiated was far from what had been promised during the referendum campaign in 2016, and the country was faced with a 'terrible' choice between 'vassalage and chaos'.
'We are barreling towards an incoherent Brexit,' he said.
The resignation is a massive blow for Mrs May - who is taking part in Armistice events in France today and apparently had no advance warning.
It comes amid mounting domestic pressure from all sides, as the DUP vows to torpedo Mrs May's government if she bows to EU demands on the Irish border 'backstop'.
It was hailed by Boris, who tweeted that he had 'boundless admiration as ever for my brother Jo'.
'We may not have agreed about Brexit but we are united in dismay at the intellectually and politically indefensible of the UK position,' he wrote.
A Downing Street spokesman dismissed the call for another national vote: 'The referendum in 2016 was the biggest democratic exercise in this country's history. We will not under any circumstances have a second referendum.
'The Prime Minister thanks Jo Johnson for his work in Government.'
Mrs May has now suffered an eye-watering 18 resignations since becoming PM in 2016 - although only a handful have been over Brexit.
Philip Lee, who is among those who did quit over the EU process, urged other Tories to show the same 'courage'.
'Following @JoJohnson's resignation I call upon my fellow MPs to show the same courage. We must allow our constituents to have a #FinalSay on Brexit. We must speak up now,' he said.
Boris's 'quieter and cleverer' younger brother who has caused a storm for May
The younger brother of Boris Johnson has been described as 'quieter and cleverer' than his older sibling.
While Boris started his education in England, Jo didn't start school until after the family had moved the Brussels when their father Stanley got a job with the European Commission.
Jo therefore first took classes as European School in Uccle in the south of the Belgian capital. Both brothers became fluent in French during their childhood years on the continent.
Both he and Boris later went to Eton College and then Balliol College, Oxford, Boris studying classics, Jo studying modern history.
Jo, like Boris, was a member of the notorious Bullingdon Club, a drinking society known for its wanton acts of drunken vandalism, and numbering Oxford's wealthiest undergraduates among its members.
Jo did his postgraduate studies in Europe and has degrees from two further European universities.
Boris went into journalism after graduating, working for the Times and the Daily Telegraph, Jo meanwhile became an investment banker at Deutsche Bank, before also becoming a journalist at the Financial Times, working in Paris and South East Asia before editing the influential finance column, Lex.
Jo married Amelia Gentleman, a reporter for the Left-wing Guardian in 2005.
The brothers both then went into politics, Boris being elected as MP for Henley in 2001.
Nine years later in 2010, Jo stood as the Conservative candidate in Orpington, south-west London and won with a 19,000 vote majority.
In a statement on his website, Mr Johnson - who had a big hand in writing the Tories' 2015 manifesto that pledged to honour the referendum result - said: 'Although I voted Remain, I have desperately wanted the Government, in which I have been proud to serve, to make a success of Brexit: to reunite our country, our party and, yes, my family too.
'At times, I believed this was possible. That's why I voted to start the Article 50 process and for two years have backed the Prime Minister in her efforts to secure the best deal for the country.
'But it has become increasingly clear to me that the Withdrawal Agreement, which is being finalised in Brussels and Whitehall even as I write, will be a terrible mistake.'
He added: 'To present the nation with a choice between two deeply unattractive outcomes, vassalage and chaos, is a failure of British statecraft on a scale unseen since the Suez crisis.
'My constituents in Orpington deserve better than this from their Government.'
Mr Johnson, who was demoted from universities minister earlier this year after a botched attempt to install Toby Young on a watchdog, called for a second Brexit referendum.
'Given that the reality of Brexit has turned out to be so far from what was once promised, the democratic thing to do is to give the public the final say,' he said.
'This would not be about re-running the 2016 referendum, but about asking people whether they want to go ahead with Brexit now that we know the deal that is actually available to us, whether we should leave without any deal at all or whether people on balance would rather stick with the deal we already have inside the European Union.'
Boris Johnson, said that although their views were starkly different, they had come to the same conclusion about the package on offer.
'This is not taking back control. It is a surrender of control. It does not remotely correspond to the mandate of the people in June 2016,' he tweeted.
Mr Johnson's sister, television personality Rachel Johnson, tweeted: 'Am hugely proud of my honourable and principled brother Jo who has put the interests of the country ahead of his political career.'
Best for Britain chief Eloise Todd urged other minister to follow suit.
'This is an incredibly brave move from Jo Johnson at a time when the public desperately needs more MPs to act in the national interest,' she said.
'We've been hurtling towards a blindfolded Brexit for too long, so it's about time that politicians hand back control to the people of this country by giving them the final say on Brexit - with the option to stay and lead in Europe.'
Brexit has proved a painful dividing in the Johnson family.
While Boris ended up spearheading the Leave campaign, both Jo and Rachel were trenchant Remainers.
Their father Stanley also fought for a Remain victory - but has since suggested he has changed his mind.
Mr Johnson senior said last month that EU commission president Jean-Claude Juncker's state of the union address, hailing the prospect of Brussels having its own army, had convinced the bloc was headed 'in a direction we don't really want to go'.