Prime Minister Theresa May will trigger Article 50 on Wednesday 29 March, starting the historic process of pulling the UK out of the European Union.
The move paves the way for two years of negotiations with the EU, meaning that the country is expected to be out of the bloc in March 2019.
It comes nine months after Britain voted to leave by a 52% - 48% majority in the 23 June referendum.
Brexit Secretary David Davis said: "Last June, the people of the UK made the historic decision to leave the EU.
"Next Wednesday, the Government will deliver on that decision and formally start the process by triggering Article 50.
"We are on the threshold of the most important negotiation for this country for a generation.
"The Government is clear in its aims: a deal that works for every nation and region of the UK and indeed for all of Europe - a new, positive partnership between the UK and our friends and allies in the European Union."
The move was announced in London after Britain's envoy to Brussels, Sir Tim Barrow, informed the office of EU President Donald Tusk in the morning.
"We want negotiations to start promptly," said Downing Street.
Shortly after the announcement, the pound dropped over two-tenths of a cent against the dollar to $1.237. It has now recovered and is currently down less than one-tenth of a cent at $1.239.
In Brussels, a spokesman for the European Commission said: "Everything is ready on this side. We are waiting for notification."
The EU is expected to release an initial response to the Article 50 notification within 48 hours. The remaining 27 leaders are also expected to call an extraordinary summit within four to six weeks.
Mr Tusk tweeted that "within 48 hours of the UK triggering Article 50, I will present the draft #Brexit guidelines to the EU27 Member States."
The notification marks the first time the Article 50 provisions, which outline the process for any EU member state to pull out of the union, have been activated.
Just days before, on 25 March, European leaders will gather in Italy to mark the 60th anniversary of the Treaty of Rome. Mrs May will not attend the celebrations.
The German Chancellor, Angela Merkel, insisted the impending notification would not overshadow the festivities to mark the EU's founding treaty.
"It makes absolutely no difference whether the notification comes one day earlier, or three or seven days afterward," she said, adding the remaining 27 nations in the coming years would look at ways to "strengthen their co-operation".
Notification of the historic step will come in the form of a letter from the Prime Minister to Mr Tusk.
Mrs May will then address MPs in a statement to the House of Commons following her regular weekly session of Prime Minister's Questions.
Over the next two years, the sides will be involved in talks that will reshape their relationship and help determine the future of Europe.
Talks over trade will be especially delicate. The issues of an exit bill - with some suggesting the UK might need to pay up to €60bn (£51bn) - and of the fate of EU citizens in Britain and British citizens on the continent will also be crucial.
Speaking to MPs on the Brexit Select Committee, Mr Davis said last week the Government had not done an assessment of the economic impact of the UK leaving the EU without a trade deal.
Mrs May has said she would rather walk away from the negotiating table than accept a bad deal.
The Article 50 announcement was made as Mrs May visits Wales as part of the Government's effort to convince the devolved nations that their input will help shape its Brexit negotiations.
The Shadow Brexit Secretary, Keir Starmer, accused the PM of failing to build the consensus she had promised around Brexit, and vowed to hold her accountable throughout the process.
"Britain is about to embark on the most complex and important negotiations since World War II, so this a hugely significant moment for the whole country," he said.
"Labour will hold the Prime Minister to account all the way, and argue for a Brexit deal that puts jobs, the economy and living standards first."