His resignation comes days after Theresa May secured the cabinet’s backing for her Brexit plan despite claims from Brexiteers it was “soft”.
Mr Davis was appointed Brexit secretary in 2016 and was responsible for negotiating the UK’s EU withdrawal.
Junior minister Steven Baker quit shortly after Mr Davis – as Mrs May prepares to face MPs and peers on Monday.
Brexiteer Conservative MP Peter Bone hailed Mr Davis’ resignation as a “principled and brave decision”, adding: “The PM’s proposals for a Brexit in name only are not acceptable.”
Labour Party chairman Ian Lavery said: “This is absolute chaos and Theresa May has no authority left.”
Labour leader Jeremy Corbyn said Mrs May was “incapable of delivering Brexit”.
No choice but resignation’ By BBC political editor Laura Kuenssberg
After many months of rumours that he would pull the plug, David Davis has actually quit as Brexit Secretary.
His unhappiness in government has been no secret for some time, but after the prime minister’s Chequers agreement with cabinet ministers to pursue looser ties with the EU than he desired, he found his position untenable.
After a visit to Downing Street on Sunday he concluded that he had no choice but to walk. It’s expected that at least one other minister will resign alongside him from the Brexit department. The move, while not completely surprising, throws doubt onto how secure the government’s Brexit strategy is.
David Davis resigning at such a crucial time shows @Theresa_May has no authority left and is incapable of delivering Brexit.
With her Government in chaos, if she clings on, it’s clear she’s more interested in hanging on for her own sake than serving the people of our country.
— Jeremy Corbyn (@jeremycorbyn) July 8, 2018