Britain is preparing to leave the European Union at 23:00 GMT with a mixture of celebration and regret.
Pro and anti-Brexit protesters have been making their voices heard at events across the country.
Prime Minister Boris Johnson – who led the 2016 Leave campaign – has called for the nation to come together in a video message.
He has hailed a “new dawn” for the UK, as European leaders warn of a tough battle ahead in trade talks.
Anti-Brexit campaigners earlier staged a march past Downing Street, to “bid a fond farewell” to the union.
Hundreds of pro-Brexit campaigners are holding a celebration rally in nearby Parliament Square, which is lined with Union flags.
Revellers sang Land of Hope and Glory and other patriotic songs – and cheered as a video showing the road to Brexit was shown on a giant screen.
Brexit Party leader Nigel Farage, who successfully campaigned for the 2016 referendum, is to address the crowd, which has also head speeches from former MEP Ann Widdecombe and Wetherspoons pub boss Tim Martin, among others.
A clock counting down to the moment the UK leaves the EU is projected on to Downing Street.
But Big Ben will not chime at 23:00 GMT due to ongoing renovation works, despite a campaign by Brexiteers for the famous “bongs” to be sounded.
In Scotland, which voted to remain in the UK, rallies and candlelit vigils are taking place, with protesters outside the Scottish Parliament, in Edinburgh, chanting: “We don’t want your Brexit”.
In a video message released on social media, an hour before Britain’s official departure, Boris Johnson said: “For many people this is an astonishing moment of hope, a moment they thought would never come.
“And there are many of course who feel a sense of anxiety and loss.
“And then of course there is a third group – perhaps the biggest – who had started to worry that the whole political wrangle would never come to an end.
“I understand all those feelings and our job as the government – my job – is to bring this country together now and take us forward.”
He said that “for all its strengths and for all its admirable qualities, the EU has evolved over 50 years in a direction that no longer suits this country”.
And his government had “obeyed the people” and “taken back the tools of self-government”.
“The most important thing to say tonight is that this is not an end but a beginning.
“This is the moment when the dawn breaks and the curtain goes up on a new act. It is a moment of real national renewal and change.”
UK citizens will notice few immediate changes as the country officially leaves the EU, after 47 years of membership.
Most EU laws will continue to be in force – including the free movement of people – until 31 December, when the transition period comes to an end.
The UK is aiming to sign a permanent free trade agreement with the EU – along the lines of the one the EU has with Canada – by that deadline.
Mr Johnson earlier held a Cabinet meeting in Sunderland, in north-east England – the city that was the first to back Brexit when results were announced after the referendum.
In Brussels, the British flag has been removed from its pole outside the European Parliament and replaced with the flag of the European Union.
Britain voted by 52% to 48% to leave the EU in a 2016 referendum, but wrangling over how to implement the result, or whether there should be another referendum, brought Parliament to a standstill.
Mr Johnson managed to secure an early general election in December last year, which he won with an 80 seat majority, on a promise to “get Brexit done”.
But opinion polls suggest the UK public remains deeply divided over the issue.
Emmanuel Macron has delivered his own address to the nation in France, describing Brexit as an “alarm signal” which should be heard across the EU.
The French president said: “At midnight, for the first time in 70 years, a country will leave the European Union.
“It is a historic alarm signal that must be heard in each of our countries.”
European Commission President Ursula von der Leyen paid tribute to UK citizens who had “contributed to the European Union and made it stronger”.
Upcoming trade negotiations would be “fair” but each side would fight for its interests, she added.
But European Council President Charles Michel warned: “The more the UK will diverge from the EU standards, the less access to the single market it will have.”
Washington’s ambassador to the UK, Woody Johnson, said Brexit had been “long supported” by President Donald Trump.
America’s “special relationship” with the UK “will endure, flourish and grow even stronger in this exciting new era which Britain is now beginning,” said Mr Johnson in a statement.
He acknowledged there will be occasional “disagreements”, but added: “Now that the UK is back in control of its own trade policy, we look forward to achieving a broad free trade agreement that will increase prosperity and create jobs in both our countries.”
Anti-Brexit campaigners have, meanwhile, demanded Northern Ireland – where a majority voted to remain in the EU – continues to have a voice in the EU after the UK leaves. at a series of protests at the border.
In a speech in Edinburgh, First Minister Nicola Sturgeon said Scotland was being “taken out of the European Union against the wishes of the overwhelming majority” of its people.
Speaking in Cardiff, Welsh First Minister Mark Drakeford said Wales, which voted to leave the EU, remained a “European nation”.
Liberal Democrat acting leader Sir Ed Davey vowed his pro-EU party would “never stop fighting” to have the “closest possible relationship” with Europe and try to prevent a “hard Brexit hurting British people”.
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