Matt Hancock replaced Hunt as health secretary, while Attorney General Jeremy Wright was appointed as minister of digital culture, media and sport, Hancock's old job. His departure adds to a crisis over Brexit that threatens to tear apart Prime Minister Theresa May's government.
Johnson said in his letter that May's plan to keep close economic ties with the bloc means Britain is heading for a "semi Brexit" that would leave Britain with the "status of a colony" of the EU.
The prime minister hammered out a compromise with her deeply divided cabinet in an all-day meeting at Chequers on Friday, but after consulting friends and allies since, Johnson decided he could not promote the deal.
Mr Johnson and Mr Davis were joined by another Brexit minister Steve Baker MP, and two parliamentary private secretary MPs Conor Burns and Chris Green. He said "the Brexit dream is dying, suffocated by needless self doubt".
She also said that the government had no intention of extending Article 50, which is a notice of intention to leave the European Union, and that there will not be a second national vote on this Brexit deal.
Johnson and Davis are two of the most prominent proponents of a so-called "hard Brexit", or a clean break with the EU.
Downing Street has been on a charm offensive with Conservative MPs since Theresa May and her Cabinet agreed a Brexit deal at Chequers on Friday - with mixed results.
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Rebuffing claims that her proposals make too many concessions to the EU, May said "this is the right Brexit" and would leave Britain free to make its own laws and trade deals.
Yet he and Johnson have shared a mutual affinity for one another, so his departure may put the already tenuous U.S. -U.K. relationship on even shakier ground, especially if May enters into conversations with Trump from a weakened position.
Brexit-backing lawmakers have been angered by May's plans, saying they will keep Britain too close to the European Union and limit its ability to strike new trade deals. "I believe that is what people voted for when they voted to leave and we will deliver in faith with the British people", she said.
Listen to Theresa May's impassioned address to Parliament today - promising a return to United Kingdom sovereignty after Brexit, yet simultaneously keeping close ties to Europe (no country with an EU association agreement has so far avoided signing up to binding relations), with frictionless trade and a close customs relationship that is not a customs union (honest), while remaining free to strike the UK's own trade deals.
Like Mr Gove - who infamously made a rival bid for the leadership after the referendum - Mr Johnson has always been suspected of aiming to lead the party and be prime minister.
The UK and the European Union have been negotiating Brexit terms for more than a year now and have been hoping to agree broad aims for their future relationship in October.
The spate of resignations has left May open to a leadership challenge from within her party that could topple the government and force an early election.