Boris Johnson is planning to hail "the dawn of a new era" in an address to the nation, one hour before Brexit.
Also today, the prime minister will hold a cabinet meeting in Sunderland - the first city to back Brexit in June 2016's EU referendum, where more than 60% voted Leave.
Official government celebrations include Downing Street being lit up with a light show, union flags flying in Parliament Square, and three million Brexit-themed 50p coins entering circulation.
Mr Johnson will remain inside 10 Downing Street throughout the evening, while the Brexit Party leader Nigel Farage leads a raucous party beneath the flags in Parliament Square.
But, despite a high-profile campaign, Big Ben will remain silent as the clock strikes 11pm.
It is 47 years since the UK joined the European Economic Community - and tonight, those bonds will be broken.
In Brussels, the UK flag will be removed from its place on the buildings housing the city's EU institutions, and one union flag is expected to be consigned to a museum.
"A moment of real national renewal"
In his video message, to be released at 10pm, Mr Johnson has promised that he will bring the country together.
He says: "Our job as the government - my job - is to bring this country together and take us forward.
"And 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.
"This is the dawn of a new era in which we no longer accept that your life chances - your family's life chances - should depend on which part of the country you grow up in.
"This is the moment when we begin to unite and level up."
