The Conservative Party Chairman has quit after the party suffered two bruising by-election defeats with a searing letter to Boris Johnson.
Oliver Dowden said the party could no longer have "business as usual" and warned: "Somebody must take responsibility" - hours after the PM said it'd be "crazy" for him to resign.
In Tiverton and Honiton, the Liberal Democrats overturned a 24,000 Tory majority to win, while Labour reclaimed Wakefield with an astonishing 12% swing.
The contests, triggered by the resignation of disgraced Tories, offered voters the chance to give their verdict on the Prime Minister just weeks after 41% of his own MPs cast their ballots against him.
In his resignation letter to the PM, Mr Dowden said: "Yesterday’s Parliamentary by-elections are the latest in a run of very poor result for our party."
“Our supporters are distressed and disappointed by recent events, and I share their feelings.
“We cannot carry on with business as usual. Somebody must take responsibility and I have concluded that, in these circumstances, it would not be right for me to remain in office.”
Boris Johnson was waking up 4,000 miles from home today to the devastating results.
Speaking to broadcasters in Kigali, the Prime Minister insisted he would keep going and thanked Mr Dowden for his service.
"It's absolutely true we've had some tough by-election results, they've been, I think, a reflection of a lot of things, but we've got to recognise voters are going through a tough time at the moment," he said.
"I think, as a Government, I've got to listen to what people are saying, in particular to the difficulties people are facing over the cost of living, which, I think, for most people is the number one issue.
"We're now facing pressures on the cost of living, we're seeing spikes in fuel prices, energy costs, food costs - that's hitting people.
"We've got to recognise there is more we've got to do and we certainly will, we will keep going, addressing the concerns of people until we get through this patch."
The Prime Minister is due to give a speech at the opening ceremony of the Commonwealth Heads of Government Meeting in Rwanda - alongside dignitaries from 54 nations and Prince Charles.
He will also give a press conference in the capital Kigali.
Speaking before the result on Thursday, the PM said it would be “crazy” for him to quit - even if he lost both by-elections.
Those comments will come under pressure after Mr Dowden's letter.
The Mirror asked how much he would be personally responsible for the results - and whether he’d throw in the towel if he lost both.
But Mr Johnson said: “Come on, it was only a year ago that we won the Hartlepool by-election.
"We hadn’t won Hartlepool for - I can’t remember when the Tory party last won Hartlepool - a long time. I don’t think it ever had.
“Governing parties generally do not win by-elections, particularly not in mid term.
“You know, I’m very hopeful, but you know, there you go. That’s just the reality.”
Asked to confirm he would not consider his position, the Prime Minister told us: “Are you crazy?”
Mr Dowden's remarks take a strikingly different tone to words he used ahead of the Prime Minister's vote of no confidence.
Ahead of the vote, he tweeted: “I will be voting for Boris Johnson in the confidence vote tonight.
“He’s demonstrated real leadership in getting the big calls right as PM – Brexit, vaccines, reopening and Ukraine.
“I hope after this vote we can come together and focus on the future. Let’s face the big challenges united and focused on delivery.”
The Liberal Democrats said their candidate Richard Foord had overturned the biggest majority in by-election history.
It was the sixth biggest swing against a government since 1945 in by-elections where both the seat and incumbent changed hands.
The new Lib Dem MP used his acceptance speech to call for Mr Johnson “to go, and go now”, claiming his victory had “sent a shockwave through British politics”.
He said: “The people of Tiverton and Honiton have spoken for Britain. They sent a loud and clear message – it’s time for Boris Johnson to go, and go now.”
He said that “every day Boris Johnson clings to office he brings further shame, chaos and neglect”.
Labour won back the Red Wall seat of Wakefield, which it had held since the 1930s but lost to the Tories in 2019.
New MP Simon Lightwood said: "The people of Wakefield have spoken on behalf of the British people.
"They have said, unreservedly: Boris Johnson, your contempt for this country is no longer tolerated."
Labour leader Sir Keir Starmer said: "Wakefield has shown the country has lost confidence in the Tories.
"This result is a clear judgment on a Conservative Party that has run out of energy and ideas. Britain deserves better."
He said the result showed Labour "is back on the side of working people, winning seats where we lost before, and ready for government".
