Sajid Javid and Rishi Sunak have both quit as ministers in a devastating blow to Boris Johnson.
Javid turned on the PM first, announcing: “I have spoken to the prime minister to tender my resignation as secretary of state for health and social care.
“It has been an enormous privilege to serve in this role, but I regret that I can no longer continue in good conscience.”
Sunak confirmed he was resigning as Chancellor moments later, saying: “I recognise this may be my last ministerial job, but I believe these standards are worth fighting for and that is why I am resigning.”
Steve Barclay will be promoted to health secretary and replace Javid, it was later confirmed.
Nadhim Zahawi -formerly the education secretary - was announced as the new chancellor of the exchequer, Downing Street said.
A number of junior ministers also quit, citing reasons including poor leadership and the recent damage to the Conservative Party's reputation.
It comes as Johnson was embroiled in yet another scandal, after he was accused of lying to cover up his knowledge of allegations of sexual misconduct against Chris Pincher before hiring him as deputy chief whip.
The double resignation leaves the PM in a perilous position amid growing restiveness on the Tory backbenches over Johnson's disregard for ministerial standards.
Both Sunak and Javid alluded to Johnson's own conduct in their letters.
Sunak suggested the government was not being “conducted properly, competently and seriously”, as he told Johnson that “our approaches are fundamentally too different”.
Javid said his decision came on the basis of his conviction that “the country needs a strong and principled Conservative Party", which Johnson was not able to offer.
Watch: Cabinet meets as PM comes under more pressure
Who has resigned so far?
Rishi Sunak - Chancellor of the Exchequer
Sajid Javid - Health Secretary
Oliver Dowden - Conservative Party Chairman (quit 24 June)
Bim Afolami - Conservative Party Vice Chairman
Jonathan Gullis - Parliamentary Private Secretary (and previous Johnson loyalist)
Saqib Bhatti - Parliamentary Private Secretary
Andrew Murrison - Trade Envoy to Morocco
Nicola Richards - Parliamentary Private Secretary
Virginia Crosbie - Parliamentary Private Secretary
Theo Clarke - Trade Envoy to Kenya
Alex Chalk - Solicitor General
Laura Trott - Parliamentary Private Secretary
Will Quince - Education Minister
Robin Walker - Schools minister
John Glen - Economic Secretary to the Treasury
Felicity Buchan - Parliamentary Private Secretary
Jo Churchill - Environment minister
Stuart Andrew - Housing minister
Reacting to the news, Sir Keir Starmer said: "After all the sleaze, the scandals and the failure, it’s clear that this government is now collapsing.
"Tory cabinet ministers have known all along who this prime minister is. They have been his cheerleaders throughout this sorry saga”.
The resignations started to come in minutes after Johnson was forced into an apology over the Pincher scandal.
The PM said sorry to "everybody who has been badly affected", adding: "I just want to make absolutely clear that there is no place in this government for anybody who is a predator or who abuses their position of power".
Downing Street had initially claimed the PM was not aware of "specific" allegations against Pincher when he gave him the job – a position they were forced to abandon when a former top civil servant revealed the prime minister had been personally briefed on the matter.
Later on Tuesday, minister Michael Ellis admitted in the House of Commons that Johnson was indeed briefed on the allegations in late 2019 – but forgot about it.
The scandal has soured the mood amongst Tory MPs, which was already fractured following Partygate.
Last month the PM narrowly survived a vote of no confidence in his leadership after 148 of his own MPs voted against him in an effort to oust him from power.
A number of rebels have renewed their calls for leadership change following the spate of resignations.
Speaking to Sky News, Conservative MP for North Thanet, Sir Roger Gale, said: “We now know from Simon McDonald that the prime minister knew everything about this and chose to try to cover it up.
“I’m sorry, that’s beyond the pale. This has gone far enough. The prime minister has to go.”
Others who previously backed Johnson have publicly changed their position.
Tory MP for Hastings and Rye Sally-Ann Hart, who supported Johnson in June’s confidence vote, has said she is no longer behind him.
She tweeted: “Considering the further revelations that have come to light, and given that the integrity of Parliament must be upheld, on behalf of my constituents of Hastings and Rye I am no longer able to support Boris Johnson as leader of the Conservative Party and prime minister.”
A number of ministers did come out in support for the beleaguered PM.
Jacob Rees-Mogg offered a staunch defence of Johnson, insisting that he had made a “minor mistake”.
“There are rumours that swirl around and some of them are false and some of them turn out to be true. But a prime minister cannot possibly govern and appoint on the basis of rumour. It simply wouldn’t be just.”
Johnson loyalist Nadine Dorries tweeted she was "100%" behind him.