However, he also reportedly threatened to resign from government on a number of occasions, most recently during talks to resolve a dispute with pro-EU Conservative lawmakers who wanted a greater say for parliament over the final Brexit deal.
With several Conservative MPs taking to social media to praise Mr Davis' announcement, it is unclear whether the Prime Minister's Brexit plan can command the support of her own party, or if she can avoid a leadership challenged triggered if 48 members of her parliamentary party send letters of no confidence to the chairman of the 1922 Committee.
The Sun newspaper's political editor Tom Newton-Dunn said on Twitter that it appeared that there was the possibility of a move against Mrs May as prime minister starting.
Davis' resignation was also accompanied by the resignation of his deputy, Brexit minister Steve Baker, according to the Telegraph.
There has been substantial disquiet among Brexiteers about the Chequers agreement proposals - shown to Germany's Angela Merkel before her own Cabinet, according to some reports - which would leave Britain effectively still inside the EU's Single Market for goods and agricultural products but outside the Single Market for services - such as it is - and subject to a "common rulebook" dictated by the European Union court, as well as bound to European Union standards on state aid, employment, and other regulations and forced to collect customs duties on the bloc's behalf, among other onerous obligations.
Mrs May had hoped that the Cabinet agreement secured on Friday at Chequers would help her deliver the "right Brexit" for the UK, with an offer to Brussels to share a "common rulebook" on goods and form a new UK-EU free trade area.
Former MP for Peterborough Stewart Jackson has left his role as a special adviser in the Government following the surprise resignation of the Brexit Secretary. Some lawmakers have already expressed their misgivings.More news: First Thailand boys rescued two weeks after being trapped in cave
Arch-Brexiteer Jacob Rees-Mogg hit out at the "defeatism" in the Government's plans, warning that he would vote against them - and suggested other Eurosceptics may do the same.
Tory Andrew Bridgen said he could not support the proposals that came out of Chequers, describing them as a breach of the red lines and that he wouldn't support it "even if the European Union were paying us for it".
A Downing Street source said MPs will continue to be briefed on the plans, and officials will explain how it does not "breach our manifesto pledges, or our Brexit red lines".
The long-serving Conservative MP was among the new intake when Tony Blair's new Labour swept to power in 1997.
Appearing on the BBC's The Andrew Marr sShow on Sunday, he said: "I'm a realist and one of the things about politics is you mustn't, you shouldn't, make the flawless the enemy of the good". But rats leaving a sinking ship is not enough, we need their captain to go, Theresa May's time is up.
On the global markets, sterling slipped by a third of a cent against the dollar to $1.3288 in early trading.