He said "the Brexit dream is dying, suffocated by needless self doubt".
The resignations are a stunning reversal from Friday's special Cabinet at Chequers when all ministers signed up and Johnson proposed a toast to the deal - even suggested a joint newspaper column with Chancellor Philip Hammond.
After two hours in the Commons defending her plans, the PM faced Tory MPs behind closed doors - with many warning her offer gave too much away.
Detailed talks were held between Number 10 and MPs on Saturday in a bid to reassure backbenchers over the Government's plans for Britain's future relationship with the European Union, while further meetings took place on Sunday and Monday lunchtime.
The former Mayor of London said May was leading the United Kingdom to a "semi-Brexit" with a strategy that would leave the country "with a status of a colony" within the European Union.
Last night he was promoted to the bigger one of foreign secretary.
Johnson said Britain was destined for a "semi Brexit" if the blueprint agreed by the Cabinet at Chequers on Friday is delivered.
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In her statement Prime Minister vowed to deliver "a Brexit that is in our national interest, the right Brexit deal for Britain". They also argued that the proposals breach several of the "red lines" that the government had set out, including a commitment to leave the EU's tariff-free customs union.
As I said then, the Government now has a song to sing. Since I can not in all conscience champion these proposals, I have sadly concluded that I must go. They have organised a highly successful Commonwealth summit and secured record global support for this Government's campaign for 12 years of quality education for every girl, and much more besides.
In recent weeks, junior ministers Phillip Lee and Greg Hands have also resigned in order to vote against government - the former over Brexit, the latter over Heathrow.
Mr David Davis replied: "Regret, really".
'Since I can not in all conscience champion these proposals, I have sadly concluded that I must go'.
"That doesn't work, somebody else could do a better job than me". I'd have to present it in Europe.
"I don't think it's a survival issue at all". May appointed staunchly pro-Brexit lawmaker Dominic Raab to replace Davis, who insisted he did not want his resignation to become a rallying cry for the prime minister's ouster.