Amber Rudd has quit the cabinet and Conservative Party saying she cannot “stand by” while “loyal 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”.
She described the sacking of 21 Tory MPs on Tuesday as an “assault on decency and democracy”.
The MP for Hastings and Rye supported Remain in the 2016 referendum.
Rudd said her resignation had been “a difficult decision”.
In her resignation letter to PM Boris Johnson she said: “I joined your cabinet in good faith: accepting that ‘No Deal’ had to be on the table, because it was the means by which we would have the best chance of achieving a new deal to leave on 31 October.
“However I no longer believe leaving with a deal is the government’s main objective.”
In response to her resignation, shadow Brexit secretary Sir Keir Starmer tweeted that Johnson’s government was “falling apart”.