Legally, Britain left the EU on January 31 but has been in a standstill transition period during fractious talks to secure a free-trade agreement with Brussels. From, January 1, 2021, EU rules will no longer apply to the British people.
Brexit has become a reality as Britain leaves Europe's customs union and single market, ending nearly half a century of often turbulent ties with its closest neighbours.
The UK's tortuous departure from the European Union takes full effect when Big Ben strikes 11:00 pm (2300GMT) in central London, just as most of the European mainland ushers in 2021 at midnight.
Brexit has dominated British politics since the country's narrow vote to leave the bloc in June 2016, opening deep political and social wounds which remain raw.
Prime Minister Boris Johnson, a key Brexit architect, said on Thursday that Britain's destiny "now resides firmly in our hands" shortly after MPs approved his trade deal with the EU.
Legally, Britain left on January 31 but has been in a standstill transition period during fractious talks to secure a free-trade agreement with Brussels, which was finally clinched on Christmas Eve.
Once the transition ends, EU rules will no longer apply, with the immediate consequence being an end to the free movement of more than 500 million people between Britain and the 27 EU states.
Customs border checks will be back for the first time in decades, and despite the free-trade deal, queues and disruption from additional paperwork are expected.
Johnson told Britons that "the destiny of this great country now resides firmly in our hands" in a statement released by his Downing Street office.
"This moment is finally upon us and now is the time to seize it."
Britain – a financial and diplomatic big-hitter plus a major NATO power – is the first member state to leave the EU, which was set up to forge unity after the horrors of World War II.
The EU has lost 66 million people and an economy worth $2.85 trillion, but Brexit, with its appeal to nationalist populism, also triggered fears other disgruntled members could follow suit.
Leaders in both London and Brussels signalled their wish to draw a line.
"It's been a long road. It's time now to put Brexit behind us. Our future is made in Europe," European Commission president Ursula von der Leyen said on Wednesday, as she signed the trade pact.
Johnson said that Thursday heralded "a new beginning in our country's history and a new relationship with the EU as their biggest ally."
Unlike in January, when flag-waving Brexiteers led by populist anti-EU former lawmaker Nigel Farage cheered and pro-EU "remainers" mourned, no formal events are planned for the end of the transition.
Public gatherings are banned due to the coronavirus outbreak, which has claimed more than 72,000 lives and infected more than 2.4 million in Britain, including Johnson himself.
But the historic moment pushed Britain's grim virus struggles from top billing in Brent-supporting newspapers, with the Daily Mail calling it a "new dawn", while the Daily Express looked forward to 11:00 pm as the country's "finest hour".
Johnson is looking not only to a future free of Covid but also of rules set in Brussels, as Britain forges its own path for the first time since it joined the then European Economic Community in 1973.
On Wednesday, he hailed regulatory approval of Oxford University and AstraZeneca's Covid vaccine, and a "new beginning" for a prosperous, more globally focused Britain.
As well as ensuring tariff and quota-free access to the EU's 450 million consumers, Britain has recently signed trade deals with countries, including Japan, Canada, Singapore and Turkey.
It is also eyeing another with India, where Johnson plans to make his first major trip as prime minister next month, and with incoming US president Joe Biden's administration.
In the short term, all eyes will be closer to home and focused on how life outside the EU plays out in practical terms.
That includes disruption at the ports, stoking fears of food and medicine shortages, as well as delays to holidaymakers and business travellers used to seamless travel in the EU.
British fishermen are disgruntled at a compromise to allow continued access for EU boats in British waters.
The key financial services sector also faces an anxious wait to learn on what basis it can keep dealing with Europe, after being largely omitted from the trade deal.
Northern Ireland's border with EU member state Ireland will be closely watched to ensure movement is unrestricted – a key plank of a 1998 peace deal that ended 30 years of violence over British rule.
And in Scotland, where most opposed Brexit, Johnson faces a potential constitutional headache from a resurgent independence movement.