The UK will officially leave the European Union at 23:00 GMT, ending 47 years of membership.
In a video message to be released an hour earlier, Prime Minister Boris Johnson - who led the 2016 campaign to leave - will call Brexit a "new dawn".
Pro and anti-Brexit demonstrations and marches are being held across the country, as the UK flag is taken down from EU institutions in Brussels.
Little will change immediately, as the UK begins a "transition period".
Most EU laws will continue to be in force - including the free movement of people - until the end of December, by which time the UK aims to have reached a permanent free trade agreement with the EU.
Labour leader Jeremy Corbyn said the country had to "move on" after Brexit and needed to "make sure we maintain good relations" with the EU and not "fall into the arms of a free trade deal with the United States".
The Archbishop of Canterbury, Justin Welby, told BBC Radio 4's Today programme the UK "must be united in a common vision for our country, however great our differences on achieving it".
Former Prime Minister David Cameron, who led the campaign to remain in the EU during the referendum, said he believed the UK could "make a success of the choice that we made".
And Brexit Party leader Nigel Farage tweeted: "At last the day comes when we break free. A massive victory for the people against the establishment."
Brexit was originally scheduled for 29 March last year but was repeatedly delayed when MPs rejected a previous withdrawal agreement reached by the EU and former Prime Minister Theresa May.
Mr Johnson got his own deal through Parliament after winning December's general election with a House of Commons majority of 80, on a pledge to "get Brexit done".
This brought to an end more than three years of political argument, following the 2016 referendum, in which 52% of UK voters backed leaving the EU.
The prime minister held a cabinet meeting at the National Glass Centre, a museum and arts centre in Sunderland, the city that was the first to back Brexit when results were announced after the referendum.
The meeting was held amid tight security. Sunderland University students posted a video on social media of a small group of protesters chanting "Boris you're not welcome here" and "Tory cuts not welcome here".
Mr Johnson told the Cabinet it was time to start a "new chapter in the United Kingdom's story" and end the division of the past three and a half years, according to a Downing Street spokesman.
The Cabinet discussed future trade deals, including seeking a a Canada-style free trade agreement with the EU, and Mr Johnson thanked Brexit Secretary Stephen Barclay for the work of his department, which is being wound up.
The PM told ministers the government aimed to have 80% of the UK's trade with other nations covered by free trade agreements within three years.
Ministers also received updates from Health Secretary Matt Hancock and Foreign Secretary Dominic Raab on measures to deal with the coronavirus.
In his video message, filmed in Downing Street, Mr Johnson will say: "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."
Supporters of the EU have taken part in a procession through Whitehall to "bid a fond farewell" to the union.
Later, Brexiteers will gather in Parliament Square for a celebration, and a clock counting down to the moment the UK leaves the EU will be projected on to Downing Street.
Buildings along Whitehall will be lit up and Union flags line Parliament Square.
A new commemorative 50p coin will also come into circulation to mark the UK's withdrawal.
However, Big Ben will not chime at 23:00 GMT due to ongoing renovation works.
Mr Johnson will host an evening reception in Downing Street for cabinet ministers, No 10 advisers, civil servants, those involved in the negotiations and supporters of the campaign to leave the EU.
They will be served English sparkling wine and a selection of canapés including fillet of lamb on toast, Shropshire blue cheese, beef and Yorkshire pudding with horseradish sauce, mushrooms tarts and roast chicken skewers.
In Brussels, the UK flag will be removed from the EU institutions, with one Union flag expected to be consigned to a museum.
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."
His predecessor, Donald Tusk, told the BBC's Andrew Marr show, in an interview to be broadcast on Sunday, that he could not see the UK rejoining the EU in his lifetime.
"This new reality will be for life. I mean for my generation," he said.
Anti-Brexit campaigners have demanded Northern Ireland - where a majority voted to remain in the EU - continues to have a voice in the EU after the UK leaves.
During one of a series of protests planned at the Irish border through Friday, Border Communities Against Brexit activists unveiled a billboard declaring the "fight goes on".
They urged the Irish government and the restored Stormont executive to push for some form of continued representation in EU structures.
In Scotland, which also voted to stay in the EU in the 2016 referendum, candlelit vigils are planned.
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".