David Cameron has announced he will be out of Downing Street within months and Jeremy Corbyn's position is in the balance after the UK voted to leave the European Union.
Senior Brexit campaigner Boris Johnson hailed the Prime Minister as a "brave and principled man" and insisted the Leave vote would give the UK a "glorious opportunity" for a brighter future.
But the immediate aftermath of the referendum result saw turmoil on the markets, with the FTSE plunging by more than 7% at one stage before recovering, while the value of sterling crashed.
The former London mayor said: "I believe the British people have spoken up for democracy in Britain and across Europe and I think we can be very proud of the result."
Despite the division between Remain-backing Scotland and Brexit-supporting England, Mr Johnson said the result "doesn't mean that the UK will be in any way less united, nor indeed does it mean we will be any less European".
He said the UK would remain a "great European power" outside the future union of 27 members.
Today's twists and turns
President Barack Obama said in a statement the UK and EU will remain "indispensable partners" of the United States.
The final results of the referendum revealed the UK voted by 52% to 48% to leave the EU.
Cameron announced he would hand over the premiership to a new Conservative leader by October.
Senior Labour MPs tabled a motion of no confidence in Jeremy Corbyn.
More than £100 billion was wiped off the FTSE 100 as the index fell more than 7%, while the pound also crashed against the US dollar before the markets regained some of the lost value after Bank of England governor Mark Carney pledged to intervene.
Nicola Sturgeon said the result was "democratically unacceptable" because Scotland had voted to Remain in the EU, and confirmed that her administration would draw up legislation to allow a second independence referendum to be held.
The Prime Minister, who staked his political future on the result of the referendum and lost, announced his decision to quit in an emotional statement in Downing Street.
His announcement will trigger a battle for the leadership - and the keys to Number 10 - likely to feature Brexit standard-bearer Johnson taking on figures such as Home Secretary Theresa May, who kept a low profile in the referendum campaign.
Announcing his resignation after six years as PM - and just 13 months after securing an absolute majority for the first time - was "not a decision I have taken lightly", said Cameron.
But he said it was "in the national interest to have a period of stability and then the new leadership required".
With his voice cracking at times, Cameron stood by his assertion that the UK could "find a way" to survive outside the EU.
"Now the decision has been made to leave we need to find the best way and I will do everything I can to help," he said.
Minutes after the PM's statement, Mark Carney announced he was making £250 billion available to support markets as he pledged that the Bank of England "will not hesitate to take additional measures as required as markets adjust and the UK economy moves forward".
Within the Labour ranks, Corbyn was the focus of anger from MPs who believe he did not campaign hard enough for a Remain vote, and from those who claim the party did not do enough to address concerns about immigration.
Senior backbencher Dame Margaret Hodge, who tabled a motion of no confidence in Corbyn, urged him to "do the decent thing" and follow Cameron's lead in quitting.
"The European referendum was a test of leadership and I think Jeremy failed that test," she told Sky News.
The motion was seconded by Ann Coffey, who told the Press Association: "The result of the European Union referendum leaves this country in a mess.
"Leaders have to take responsibility and he has to take his share of responsibility for this, and he should resign."
US President Barack Obama has insisted the "special relationship" between the UK and Washington will endure following the Brexit referendum result.
Washington had hoped the UK would remain in the EU, and Obama used a high-profile visit to London to warn that Britain would be at the "back of the queue" for a trade deal in the event of Brexit.
But in a statement issued by the White House following the historic referendum result, Obama said both the UK and European Union would remain "indispensable partners".