The Eurosceptic foreign secretary was holed up in his official residence for most of the day before finally deciding to quit, missing a summit on the West Balkans, which he was due to host, as well as an emergency Cobra meeting to discuss the Salisbury poisoning.
The news came hours after Mr Davis’s resignation as the Brexit secretary, with both men understood to be deeply unhappy with the prime minister’s new Brexit plan, which was agreed at a crunch summit at her Chequer’s retreat on Friday.
But what does this mean for the beleaguered prime minister?
Is the government collapsing?
In a word, no. Ms May still has a mandate and the support of much of her party, but these resignations have made her vulnerable.
Mr Johnson and Mr Davis are both big figures in the Conservative party, and Ms May has long been too weak to sack the ex-foreign secretary – despite a serious of humiliating and damaging gaffes.
Both men are leading Brexiteers, which carries plenty of weight with the powerful Eurosceptic wing of the party.
Ms May has lost seven cabinet ministers in the past year – a record which would undoubtedly have toppled another politician.
However the lack of a credible successor to the leadership has acted in her favour.
What happens next?
In an excruciating bit of timing, Ms May is due to address the 1922 committee of backbench Tory MPs this evening, to convince them of the merit of her Brexit strategy.
Her authority has taken a battering and she will be looking to test the mood among colleagues.
She needs their support as prime ministers can be toppled by their backbench MPs through a no-confidence motion, which would then trigger a leadership contest.
However Eurosceptic MPs told The Independent that their concerns were with “policy not personnel”, suggesting Mr Johnson’s departure may not be the death knell of her premiership.
What needs to happen to bring about a motion of no confidence in the PM?
Tory rules require 15 per cent of the parliamentary party – or 48 MPs – to write to Sir Graham Brady, the chairman of the 1922 committee, to express no confidence in the prime minister.
The influential committee would oversee a leadership contest, where any Tory MPs can be stand, before a decision over the final two is taken by party members.
A contest could also be brought about if the PM decides to resign.
But, asked if Ms May would fight any attempt to remove her through a vote of no confidence, a senior Downing Street source said: “Yes.”
Who would be in the frame for a leadership battle?
Plenty of Tory MPs could throw their hats in the ring.
Michael Gove, the environment secretary, and Sajid Javid, the home secretary, are both seen as front runners.
Defence secretary Gavin Williamson could also have a tilt, and Jeremy Hunt, the health secretary, who is riding high after winning £20bn for the NHS.
Liz Truss, chief secretary to the Treasury, Penny Mordaunt, the Brexit-backing international development secretary, and Ms May’s former rival, Andrea Leadsom, could all also put themselves forward.
Question marks remain over both Mr Johnson and Mr Davis, now they are both free from loyalty to Ms May.
Will there be a general election?
The Fixed-Term Parliaments Act made it much harder to call an early general election.
It can only be done if a motion is agreed by two thirds of the Commons or if a no-confidence motion is passed and no alternative government is put forward within 14 days.
Conservative MPs are unlikely to be keen on a fresh poll after last year’s bruising snap election, where Jeremy Corbyn’s Labour party saw a surge in popularity.
Bookies have now slashed the odds of a 2018 election from to 6/4 from 5/1, but a number of hurdles need to be passed before it seems like a reasonable prospect.