Amber Rudd has quit the cabinet and surrendered the Conservative whip saying she cannot “stand by” while “moderate Conservatives are expelled”.
The work and pensions secretary said she no longer believed leaving the EU with a deal was the government’s “main objective”.
Ms Rudd described the sacking of 21 Tory MPs on Tuesday as an “assault on decency and democracy”.
No 10 said it was “disappointed” by the resignation of a “talented” minister.
But a spokesperson added that “all ministers who joined the Cabinet signed up to leaving the EU on 31 October come what may”.
Ms Rudd’s resignation comes as PM Boris Johnson is reportedly considering defying a new law aimed at forcing him to seek an extension to the Brexit deadline if he fails to secure parliamentary approval on an exit agreement by 19 October.
A senior No 10 source told The Sunday Times: “If there isn’t a deal by the 18 [October] we will sabotage the extension.”
According to the Sunday Telegraph, Downing Street says Mr Johnson “does not share the rebel interpretation” of the new law, expected to gain royal assent next week, which was drawn up by cross-party MPs, including 21 Tory rebels who have since been ousted from the party.
It is thought that Mr Johnson believes he could legally disregard some or all of the bill’s requirements – a move that could see him hauled before the courts and potentially facing prison.
It’s thought this could trigger an emergency judicial review by the Supreme Court next month, leading to a court showdown over whether the UK would be able to leave the EU with no deal on 31 October.