Boris Johnson has insisted the UK "will succeed" after Brexit but admits there will be "bumps in the road" ahead of the historic moment.
Britain is now on the final countdown to leave Europe, more than three years after the nation voted for Brexit.
Prime Minister Johnson sought to ease the "anxiety and loss" felt by many, in his address to the nation, but urged people to embrace the "astonishing moment of hope".
After years of bitter wrangling since the 2016 referendum, Mr Johnson said his job was now to "bring this country together".
"We want this to be the beginning of a new era of friendly cooperation between the EU and an energetic Britain, a Britain that is simultaneously a great European power and truly global in our range and ambitions.
"And when I look at this country's incredible assets, our scientists, our engineers, our world-leading universities, our armed forces, when I look at the potential of this country waiting to be unleashed I know that we can turn this opportunity into a stunning success.
"And whatever the bumps in the road ahead I know that we will succeed."
The departure is the result of the 2016 referendum, in which 52% of Britons voted to leave the EU after more than four decades of partnership.
An 11-month transition period will now begin, with Westminster attempting to thrash out a fresh trade agreement with Brussels before the end of December.
In the meantime dozens of Brexit fans are celebrating at Westminster for a Brexit celebration to mark the occasion.
A music system was set up on the back of a lorry on Parliament Street, with people dancing in a closed-off section of the road to music by Sir Tom Jones and Queen.
Dozens of people gathered around the Sir Winston Churchill statue, while others rang bells and banged a drum attached to a modified cart called Little Ben.
Elsewhere pro-EU supporters did their best to show their regret at the UK's exit from the European Union.
The White Cliffs of Dover was the setting for a massive message of goodwill to Europeans, with campaign group Led By Donkeys projecting an EU star onto the chalk face of the Kent coast.
“We still love EU” could be seen from out to sea as the light faded on Brexit Day.
Very little will change at the moment of Brexit as a result of a deal, which Mr Johnson agreed with Brussels and the 27 remaining member states late last year.
On the United Kingdom's final day in the EU, the prime minster was joined by Cabinet colleagues in Sunderland.
The north east city was the first in the country to return a vote to leave the European Union.
- Watch the moment a British flag gets removed from the European Council building in Brussels
Downing Street said the PM and his team discussed the government's future trade agenda, which includes seeking a free trade agreement with the EU.
As the clock strikes 11pm, Britain's MEPs will lose their seats in the Strasbourg parliament and have to go back to normal lives.
On Friday afternoon, a pro-EU banner was unveiled on Westminster Bridge by campaigners mourning the UK departing from the trade bloc. Smoke flares were also set off during the protest.
The banner read: "Here to Stay. Here to Fight. Migrants In. Tories Out."
As 11pm arrives, Big Ben will remain silent, despite a high-profile campaign fuelled by Mr Johnson, for repair works to be halted to allow Parliament’s bell to ring.
From street parties to candle lit vigils in parts of the country which voted to remain.
Downing Street will be illuminated with a light show and a new 50p coin will enter circulation.
In Brussels, the UK flag will be removed from the EU institutions, with one Union flag expected to be consigned to a museum.
In Scotland, which voted to stay in the EU in the 2016 referendum, candlelit vigils are planned.
With the UK on the final countdown to leave the EU, here's what's Boris Johnson's senior advisor and former Vote Leave director Dominic Cummings had to say: