The clock will tick down to 23:00 GMT, while Prime Minister Boris Johnson will give a “special” address to the nation in the evening, the government said.
A special 50p coin will also enter circulation to mark the occasion.
Meanwhile, a campaign to find £500,000 to make Big Ben ring when the UK leaves the EU has raised more than £200,000.
Millionaire businessman Arron Banks and the Leave Means Leave group have donated £50,000 to the campaign.
Downing Street has said the prime minister will chair a cabinet meeting in the north of England during the day, to discuss spreading “prosperity and opportunity”.
He will then make a special address to the nation in the evening.
Mr Johnson is expected to be one of the first people to receive one of the newly-minted 50p coins, which will bear the motto “peace, prosperity and friendship with all nations”.
Buildings around Whitehall will be lit up to mark Brexit, with the government saying that, “in response to public calls, the Union Jack will be flown on all of the flag poles in Parliament Square”.
The government says it will use the “significant moment in our history” to “heal divisions, re-unite communities and look forward to the country that we want to build over the next decade.”
However, it is not certain whether Big Ben – which is currently out of action due to renovation work going on at the Houses of Parliament – will chime to mark the moment the UK leaves the EU.
Earlier this week, Mr Johnson told BBC Breakfast he wanted the public to raise funds to ensure this can happen.
The House of Commons Commission estimates the cost will be up to £500,000, and it has raised concerns over using donations to fund the project.
It says this would involve bringing back the chiming mechanism and installing a temporary floor, resulting in delays to the conservation work.
But the campaign group Stand Up 4 Brexit set up an online appeal to raise the money, collecting more than £200,000 by Friday evening.
‘Inflated the figure’
Conservative MP Mark Francois told BBC Radio 4’s The World at One that the pro-Brexit Leave Means Leave campaign and Mr Banks had donated £50,000.
He queried whether the cost of getting the bell to ring again was really £500,000, adding that he believed officials had “deliberately inflated the figure” because “they don’t want to do it”.
It comes as Downing Street has said EU citizens will not automatically be deported if they fail to sign up to the settled status scheme by the 2021.
Under the settlement scheme, EU citizens living in the UK can apply to stay in the country after Brexit.
So far the number of applicants to the scheme has hit more than 2.7 million.
UK voters backed leaving the EU by a margin of 52% to 48% in the June 2016 referendum.