Johnson is the second major Brexiteer to resign in two days, following Brexit Secretary David Davis, who turned in his papers on Sunday. His promotion within the cabinet is considered an olive branch to die-hard Brexit supports. He pointed out that while some Brexiteers want to leave the customs union and single market, others advocating for a so-called "soft Brexit" want to stay.
Matt Hancock replaced him at the Health Department, with Jeremy Wright, former Attorney General, being drafted in to fill Hancock's empty position. "It is with sadness that I step down" - and he then posted an image of his resignation letter to May.
Theresa May giving a statement to the the House of Commons on Brexit after Davis and Johnson quit (Picture: AFP)Will there be a leadership challenge? "That dream is dying, suffocated by needless self-doubt".
'His replacement will be announced shortly.
Britain's Prime Minister Theresa May leaves Downing Street in London, Britain, July 10, 2018.
Johnson's abrupt departure comes two years after May took charge.
But she warned that if the European Union did not engage with her plan, there was a "serious risk" of the United Kingdom leaving in March 2019 without a deal in a "disorderly" manner.
Davis resigned late on Sunday, saying he was not willing to be a "reluctant conscript" to her plans that were agreed by the whole cabinet on Friday.
But as Foreign Secretary in May's government, he was prone to gaffes and criticized for not being on top of his brief.
The slew of resignations could possibly point to members of Parliament demanding a vote of no confidence in May, even though her team is confident that their Brexit plan would pass if it gets put to a vote.
Just 48 hours ago, the former Vote Leave leader's position was that while May's customs plan, which would keep us bound by European Union rules in perpetuity, was a "turd", he was still willing to sell it.
"We must have collective responsibility", Johnson wrote to May.
May appeared in Parliament earlier on Monday afternoon to defend her plan, minutes after Downing Street confirmed the departure of Johnson. With Johnson out, Corbyn sharpened his criticism further.
Over two long years, he and the British public have discovered just how untenable that vision was.
There was a crisis in government, he said, adding: "It is clear this government can not secure a good deal for Britain".
Theresa May faces a mortal threat to her leadership of the Conservative Party and Government today.
While other senior ministers rallied round her after the resignations which left Westminster reeling on Monday, rumblings of discontent among rank and file lawmakers remained.
"How's that going?" a minister could be heard adding, amid the peals of laughter.
Still, Johnson's exit seems to have caught many by surprise. Before news of his resignation began to circulate, the government's website had touted his announcement of an aid program as part of Johnson's attendance of the Western Balkans Summit, which the U.K.'s Foreign Office is hosting this week.