British Secretary of State for Exiting the European Union (Brexit Minister) David Davis. Photo: AFP
His resignation comes days after Theresa May secured the cabinet's backing for her Brexit plan despite claims from Brexiteers that it was too "soft".
Mr Davis was appointed Brexit secretary in 2016 and was responsible for negotiating the UK withdrawal from the EU.
A Brexiteer hailed his resignation as a "principled and brave decision".