Agriculture minister George Eustice quit after the Prime Minister bowed to Cabinet pressure to allow MPs a vote on delaying Brexit.
In a hard-hitting resignation letter, he stressed he had remained in Government despite a “series of rather undignified retreats” already.
But he now felt that Parliament – rather than the Prime Minister and her government – is “in direct control of events”.
He added: “I fear that developments this week will lead to a sequence of events culminating in the EU dictating the terms of any extension requested and the final humiliation of our country.”
French president Emmanuel Macron has warned that the EU would only agree to an extension if the UK can give a good reason for the extra time to resolve the Brexit crisis.
Leave supporter Mr Eustice, a long-term anti-EU campaigner who was part of the campaign against Britain joining the euro, also lashed out at Brussels for the tough and unified negotiating stance it has taken, which has contrasted with the civil war raging in the Tory Party.
He argued that Britain should be prepared to quit with no deal despite the predicted economic and social turmoil which the Government says could be unleashed.
“I do not believe that the (European) Commission has behaved honourably during these negotiations,” he said.
“They have deliberately made progress slow and difficult. They have stated in terms that they will refuse to even hold substantive negotiations on a future partnership until after we leave.
“If the position of Parliament is now that we will refuse to leave without an agreement then we are somewhat stuck. This is uncomfortable for everyone, but we cannot negotiate a successful Brexit unless we are prepared to walk through the door.”
His words highlighted how the Government was forced by Brussels to retreat on a series of initial demands including that the future trade deal should be negotiated in parallel with the “divorce” agreement, a move which is seen to have significantly undermined the UK’s position.
Mr Eustice’s resignations comes after a series of other departures including two Brexit Secretaries, David Davis and Dominic Raab, and Boris Johnson as Foreign Secretary.
As he left, he also took a swipe at MPs who have refused to back Mrs May’s Brexit blueprint.
“I appreciate that you have been terribly undermined by those in Parliament who refuse to respect the referendum result,” said the Camborne and Redruth MP.
He pledge to vote for the Withdrawal Agreement after backing Mrs May’s Chequers blueprint which was blocked by other Brexiteers.