Now another senior minister has quit his government — and the ruling Conservative Party — in protest at Johnson's efforts to lead the U.K. out of the European Union on Oct. 31 with or without a deal.
Amber Rudd resigned Saturday, piling more pressure on the increasingly embattled prime minister.
Johnson expelled 21 members of his own party Tuesday after they supported an opposition plan to try to block a "no deal" Brexit.
Rudd, a former interior minister who voted to remain in the E.U. in the June 2016 referendum, said the ousting of the rebel lawmakers was an "assault on democracy" and an "act of political vandalism."
"I cannot stand by as good, loyal moderate Conservatives are expelled," she said in a tweet announcing her decision.
Johnson swept to power in July, uniting the party around his leadership after Theresa May's failure to solve the country's Brexit impasse.
As lawmakers returned from summer recess, he began the week dismissing accusations from protesters in the London streets that he had conducted a coup — such was the seemingly decisive nature of his power grab to suspend Parliament until mid-Octoberin an effort to clear the way for his hardline Brexit plans.
But in a sign of how things have turned, the prime minister was forced to insist he would not himself resign.
"That is not a hypothesis I'm willing to contemplate," he said Friday during a visit to a farm in Scotland.
Rudd's resignation is the latest sign that Johnson's uncompromising approach to Brexit, an issue that has obsessed the country and paralyzed its politics, could break his party and threaten his tenuous hold on power.
Those who were kicked out of the party last week included the longest sitting lawmaker in the House of Commons and the grandson of Winston Churchill.
The prime minister's little brother, Jo Johnson, quit on Thursday.
"In recent weeks I've been torn between family loyalty and the national interest," the junior minister said on Twitter.
Jeremy Hunt, the former foreign minister who finished as a runner-up to Johnson in the leadership race earlier this summer, said Sunday that Rudd's resignation was "desperately sad news."
"When she and other brilliant people like Jo Johnson feel they can't take the whip on top of the loss of so many other distinguished colleagues this week, we must pause for thought," he said.
As politicians, commentators and experts alike scramble to assess the prime minister's dwindling options — bringing a vote of no confidence in his own government has been raised as a potential last, desperate course of action — Johnson pushed ahead with his election demands.
The bill forcing him to request a further extension to the U.K.'s divorce date with the E.U — possibly until January 2020 — is expected to become law on Monday.
Johnson says he would rather be "dead in a ditch" than request an extension.
His government says it will therefore again attempt to force an election in order to avoid an embarrassing climbdown or more drastic measures, including breaking the law.
But his election efforts continue to be rebuffed.
Opposition parties don't want to agree to a vote unless they can ensure Johnson can't take Britain out of the E.U. without a deal.
In an effort to pressure them into granting a snap election before Johnson's "do or die" deadline at the end of October, the government has sought to brand opposition Labour Party leader Jeremy Corbyn a coward.
Johnson's team even distributed pieces of chicken to the Westminster press Friday in boxes bearing Corbyn's face and the letters "JFC."
The Conservative Party also shared a mocked-up image of Corbyn dressed in a yellow chicken suit.
The gambit sparked outrage from some lawmakers, who derided it as "playground behavior" amid what many see as a national crisis.