The UK has officially left the European Union after 47 years of membership - and more than three years after it voted to do so in a referendum.
The historic moment, which happened at 23:00 GMT, was marked by both celebrations and anti-Brexit protests.
Candlelit vigils were held in Scotland, which voted to stay in the EU, while Brexiteers partied in London's Parliament Square.
Boris Johnson has vowed to bring the country together and "take us forward".
In a message released on social media an hour before the UK's departure, the prime minister 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".
"The most important thing to say tonight is that this is not an end but a beginning," he said, and "a moment of real national renewal and change".
Brexit parties were held in pubs and social clubs across the UK as the country counted down to its official departure.
Hundreds gathered in Parliament Square to celebrate Brexit, singing patriotic songs and cheering speeches from leading Brexiteers, including Nigel Farage.
The Brexit Party leader said: "Let us celebrate tonight as we have never done before.
"This is the greatest moment in the modern history of our great nation."
Pro-EU demonstrators earlier staged a march in Whitehall to bid a "fond farewell" to the union - and anti-Brexit rallies and candlelit vigils were held in Scotland.
Other symbolic moments on a day of mixed emotions included:
--The Union flag being removed from the European Union institutions in Brussels
--The Cabinet meeting in Sunderland, the first city to declare in favour of Brexit when the 2016 results were announced
--A light show illuminating 10 Downing Street and Union flags lining The Mall
--A 50p coin to mark the occasion entering circulation
In Northern Ireland, the campaign group Border Communities Against Brexit staged a series of protests in Armagh, near to the border with the Irish Republic.
The Irish border - now the UK's land border with the EU - was a major sticking point in the Brexit divorce talks.
NI and the Irish Republic "will continue to remain neighbours", said NI First Minister Arlene Foster on RTÉ on Friday.
At 23:00 GMT, Scotland's First Minister Nicola Sturgeon tweeted a picture of the EU flag, adding: "Scotland will return to the heart of Europe as an independent country - #LeaveALightOnForScotland".
Ms Sturgeon is calling for a new referendum on Scottish independence, arguing that Brexit is a "material change in circumstances".
Speaking in Cardiff, Welsh First Minister Mark Drakeford said Wales, which voted to leave the EU, remained a "European nation".
Labour MP Hilary Benn, who chairs the Brexit select committee and backed Remain, said he was "sad last night... but we have to accept it".
The UK was "always reluctant Europeans", he told BBC Radio 4's Today programme, adding: "We joined late and we left early."
What now? It's happened.
A dreary night didn't discourage those celebrating in Parliament Square. We wake this morning out of the European Union. But we follow their rules until the end of the year, without a say.
We are separate after more than 40 years, but remember much of the status quo will hold for now - the UK and the EU, the awkward couple, finally divorced - but still sharing a house and the bills.
But what the prime minister hails as a new era, a bright new dawn, starts months of hard bargaining with our neighbours across the Channel.
The UK's requests: a free trade agreement, cooperation on security, and new arrangements for fishing are just some of the vital arguments that lie ahead.(BBC)