Way back in June 2016, May campaigned for a Remain vote at the EU referendum. But a lot has changed in the interim and the vicar's daughter from Sussex now finds herself at the top of UK's political pile declaring "Brexit means Brexit".
The UK commentariat often describe the 60-year-old as a "safe pair of hands". The next two years will put that reputation to the test as Britain attempts to carve out a clean exit deal from the EU.
May's still fairly new to Number 10, but if she fails to deliver on her promises – or leaves the country in dire straights – the ruthless Conservative Party will undoubtedly launch a coup d'etat.
Nick Timothy and Fiona Hill
The six-figure-salaried super-spads are May's closet aides in Number 10. Timothy, who hails from Birmingham, and Hill, a former journalist from Scotland, both worked for May at the Home Office and were brought back into Team May after she succeeded David Cameron in July 2016.
Timothy is reportedly behind May's plans to expand grammar schools across England, while Hill was the driving force for the creation of the Modern Slavery Act. The Home Office was known as a ministerial graveyard before May came along, a testament to the Conservative premier's survivability and her advisers' skills.
Sir Jeremy Heywood
Long-time civil servant Sir Jeremy Heywood, 55, will attempt to steer Britain's bureaucracy through what are expected to be choppy waters, with Brexit will hitting all areas of Whitehall – from transport, health and defence to the environment.
Just like May, Philip Hammond backed Remain at the EU referendum before the former Foreign Secretary moved into Number 11 in July 2016.
Hammond, 61, is known as "Spreadsheet Phil" around Westminster, but his Spring Budget caused much excitement and embarrassment when the Chancellor was forced to U-turn over an unpopular plan to hike National Insurance Contributions for the self-employed.
The Brexit talks give Hammond the opportunity to get his political mojo back and boost his support among Tory backbenchers.
Davis arguably landed his dream job when May appointed him Secretary of State for Exiting the EU. The former Europe minister saw his career decline after losing out to a youthful Cameron in the 2005 Conservative leadership election.
But the referendum campaign saw Davis in the limelight again. Interestingly, the 68-year-old was not part of the lead campaign Vote Leave – like Boris Johnson and Michael Gove – and instead appeared at Grassroots Out events alongside Ukip's Nigel Farage and Labour MP Kate Hoey.
Sir Tim Barrow
When Sir Ivan Rogers quit as the UK's chief representative to the EU, Sir Tim Barrow was drafted in.
As the former political director of the Foreign Office to Brussels, Barrow knows the EU well and he will be hand-delivering the Article 50 notification to EU Council chief Donald Tusk on Wednesday.
The Oxford University graduate used to be the UK's main man in Moscow and was knighted in 2015 for "managing the complex and important relationship between the UK and Russia during an unprecedented period".
Jeremy Corbyn was a well-known Eurosceptic in the frame of socialist firebrand Tony Benn until the EU referendum. Corbyn sided with the vast majority of his MPs and backed a Remain vote at the historic ballot. But despite the left-winger's change of heart, he faced criticism for a lacklustre campaign.
He has most recently seen Labour drop to up to 18 points behind the Conservative in the opinion polls. However, Corbyn remains leader of the official opposition and his Shadow Brexit Secretary Sir Keir Starmer laid out six key tests for May's government on Monday.
Nick Clegg, Tony Blair and Open Britain
Open Britain was formed out of the ashes of the unsuccessful Britain Stronger In Europe campaign following the Brexit vote. Despite the defeat, the group has continued to hold the government to account, with a series of press conferences and stunts including a "Brexit Contract".
Former Deputy Prime Minister and Liberal Democrat MP Nick Clegg has been one of Open Brian's most prominent spokespeople and ex-Labour Prime Minister Tony Blair added his voice to the group in February.
"You can like the messengers or not like the messenger and this is a free country so I've got a right to speak and you've got the freedom to listen or not," Blair said. "I know there will be a volley of abuse that will come my way, but I'm speaking because I believe in it and I care about the country."
The First Minister of Scotland has turned up the heat on May by calling for a second Scottish independence referendum between Autumn 2018 and Spring 2019.
Scots rejecting splitting from the rest of the UK in 2014, but they also voted to Remain in the UK at the EU referendum.
May's decision to honour the UK-wide Brexit vote has emboldened Sturgeon as she seeks to trump her predecessor as SNP leader, Alex Salmond, and secure Scottish independence.