Mr Johnson’s leadership of the Tory Party suffered a double blow as voters rejected the Conservatives in two crunch by-elections.
In Tiverton and Honiton the Liberal Democrats overturned a 24,000 Tory majority to win, while Labour reclaimed Wakefield.
The contests, triggered by the resignation of disgraced Tories, were widely seen as a chance for voters to give their verdict on the Prime Minister.
The national picture looks bleak for Mr Johnson, as the damaging defeats come just weeks after 41 percent of his own MPs cast their ballots against him.
This morning, Oliver Dowden has resigned as chairman of the Conservative Party.
He said in a letter to Mr Johnson that “someone must take responsibility” for the state the Tories find themselves in.
Mr Dowden wrote: “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.”
A dramatic swing of almost 30 percent from the Tories to the Lib Dems saw Richard Foord secure a majority of 6,144 in Tiverton and Honiton.
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”.
Mr Foord 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 “every day Boris Johnson clings to office he brings further shame, chaos and neglect”.
Lib Dem leader Sir Ed Davey said: “This should be a wake-up call for all those Conservative MPs propping up Boris Johnson.
“They cannot afford to ignore this result.”
He said it was “time for Conservative MPs to finally do the right thing and sack him”.
In Wakefield, Simon Lightwood was elected with a majority of 4,925 on a swing of 12.7 percent from the Tories to Labour.
The previous Wakefield MP Imran Ahmad Khan quit after being found guilty of sexually assaulting a 15-year-old boy – a crime for which he was jailed for 18 months.
Wakefield was one of the so-called red wall seats won by the Tories in the 2019 general election after being Labour since the 1930s.
Mr 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”.
Mr Johnson, who is at a Commonwealth leaders’ summit in Rwanda, suggested it would be “crazy” for him to quit if the party lost the two seats and said mid-term by-elections were “never necessarily easy for any government”.
Boris Johnson was in Rwanda when the by-election results were announced
Oliver Dowden resigned as Conservative Party Chairman after the results were confirmed
House of Commons