Shortly after the Leave campaign secured a 51.9% majority, a tearful David Cameron announced his intention to resign before October.
As the results came in the pound plummeted to a 31-year low, while £122bn (8%) was wiped off the FTSE 100 in the minutes after it opened.
Bank of England governor Mark Carney said the UK was “well prepared” for the fallout of the Leave vote and that he would “not hesitate to take any additional measures required” to ensure financial stability.
Mr Cameron tried to reassure the markets in a statement outside Number 10 – and said he would remain in place to “steady the ship” over the coming weeks and months.
The Prime Minister said he would leave it to his successor to invoke Article 50 of the Lisbon Treaty, which kicks off the two-year process of negotiating a new trade relationship with the UK’s former partners.
Nicola Sturgeon has confirmed she wants a second independence referendum within this period to prevent Scotland – where all local authorities voted Remain – being taken out of the EU “against its will”.
The First Minister said she would “begin to prepare the legislation” to allow this to happen.
Attention will now turn to who will replace Mr. Cameron in Number 10 – with Leave campaign figurehead Boris Johnson installed as the bookies’ favourite.
He told a news conference he was “sad” the Prime Minister was stepping down and described him as “one of the most extraordinary politicians of our time”.
But the former London mayor said the UK had a “glorious opportunity” to control its own taxes and borders and “find our voice in the world again”.
Meanwhile, Labour MPs have submitted a no-confidence motion in leader Jeremy Corbyn after criticism of his efforts in the Remain campaign.
Mr Corbyn told Sky News earlier he would not resign.
The first party leader to speak after the declaration was UKIP’s Nigel Farage, who labelled 23 June “independence day” and demanded the creation of a “Brexit government”.
Reaction is also emerging from the continent, with European Council President Donald Tusk admitting the EU would have to reflect on its own future.
He tweeted: “A serious even dramatic moment, especially for the UK.
“We are prepared for this negative scenario. There will be no legal vacuum.
“On behalf of all 27 leaders: we are determined to keep our unity as 27.
“I have offered an informal meeting of the 27 in the margins of the European Council summit next week.
“I will also propose to leaders that we start a wider reflection on the future of our Union.”
The result also exposes divisions across the UK, with Leave performing strongly in the English shires, Wales and north eastern towns and cities like Sunderland, Middlesbrough and Hartlepool.
Remain secured decisive majorities in London, Scotland and Northern Ireland.
Sinn Fein sources said Brexit should lead to a poll on Irish unity, after Northern Ireland voted by 56% to 44% to Remain.
The turnout was 72.1% – the highest in a national poll since the 1992 general election.
A total of 33,577,342 voted – 17,410,742 for Leave and 16,141,241 for Remain.
A petition calling for a second EU referendum because the turnout was below 75% and the majority below 60% has attracted more than 100,000 signatures.
A separate petition calling for London to stay in the EU is being shared via the #LondOut hashtag.