Possible contenders. ─ AFP
She had been under growing pressure to quit following months of political paralysis over Brexit, which have intensified in recent weeks following disastrous results in the May 2 English local elections.
The Conservatives are expected to fare similarly badly in this week's European Parliament elections when the results are announced late Sunday.
'One last roll of the dice'
May's latest effort to force through her despised Brexit deal, which included giving MPs the option of holding a referendum on the agreement, proved her final undoing.
The move prompted a furious reaction from Conservatives — including cabinet members.
"I thought she deserved one last roll of the dice. But she took those dice and threw them off the table," a senior minister told The Times.
The clamour for her to stand down reached fever pitch after Andrea Leadsom — one of cabinet's strongest Brexit backers — resigned on Wednesday from her post as the government's representative in parliament.
She became the 36th minister to quit May's dismally dysfunctional government — a modern record.
In her resignation letter Leadsom told the prime minister she no longer believed her approach to Brexit would deliver on the 2016 referendum result to leave the EU.
Several senior cabinet ministers reportedly then held "frank" talks with May on Thursday.
No deal?
May's departure will kickstart a Conservative Party leadership contest — already unofficially underway — that is expected to be encompass more than a dozen candidates and favour a Brexiteer.
That could lead to Britain, which has already twice delayed its departure from the European Union, opting to leave the bloc without a deal on October 31, the extended deadline agreed with Brussels last month.
Tory MPs will hold a series of votes to whittle the contenders down to a final two that will be put to the party's more than 100,000 members.
Former foreign secretary and gaffe-prone Brexit cheerleader Boris Johnson is the membership's favourite, but a considerable number of Conservative MPs are thought to hold serious reservations about his suitability for the top job.
He has repeatedly said Britain should not fear a so-called no-deal Brexit.
'No legacy'
May was the surprising victor in a 2016 leadership contest to replace predecessor David Cameron after he resigned in the aftermath of the Brexit referendum
Despite having campaigned to stay in the EU, she embraced the cause with the mantra "Brexit means Brexit".
However the decision to hold a disastrous snap election in June 2017, when she lost her parliamentary majority, left her stymied.
May will leave office without any significant achievements to her name — other than the bungled handling of Brexit, according to political analysts.
"She doesn't really have a legacy that she can call her own other than just having to manage what is a very difficult issue," said Simon Usherwood, from the University of Surrey's politics department.
"I think anybody in her position would have had great difficulty."
Others were more brutal in their assessment.
"It was only an impossible job because she made it one," said Tim Bale of Queen Mary University of London.