Theresa May has vowed to “negotiate hard” as Downing Street announced Article 50 would be triggered on 29 March.
The official notification will be sent to European Council President Donald Tusk next Wednesday, starting the formal process of leaving the EU.
The move will pave the way for two years of negotiations, with the country expected to be out of the bloc by the end of March 2019.
Speaking during a visit to Swansea, Mrs May said: “I am very clear that I want to ensure we get the best possible deal for the United Kingdom.”
The PM promised to work on a deal “that works for everyone across the United Kingdom and all parts of the UK”.
“I have set out my objectives,” she said. “These include getting a good free trade deal. They include putting issues like continuing working together on issues like security at the core of what we are doing.
“We are going to be out there, negotiating hard, delivering on what the British people voted for.”
The Article 50 announcement came after Britain’s envoy to Brussels, Sir Tim Barrow, informed Mr Tusk’s office on Monday morning.
Brexit Secretary David Davis said triggering Article 50 would initiate “the most important negotiation for this country for a generation”.
He said the Government wanted to secure “a new, positive partnership between the UK and our friends and allies in the European Union”.
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 to give a mandate for European Commission chief negotiator Michel Barnier, with talks probably beginning in earnest in May or June.
Mr Tusk tweeted that he plans to present draft Brexit guidelines to the remaining 27 member states within 48 hours of notification.
The negotiations will cover a wide range of subjects and seek to disentangle Britain after more than 40 years of integration.
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.
Commission President Jean-Claude Juncker warned that London may have to abandon hopes of a trade deal unless it accepts the terms offered by the EU, which are widely expected to include a hefty divorce bill.
The UK will have “the choice to eat what’s on the table or not come to the table at all”, Mr Juncker told German newspaper Bild am Sonntag.
The Scottish government, which wants a second independence referendum, complained it had not been informed of the announcement in advance.
Labour leader Jeremy Corbyn said: “The Government has failed to build a consensus about what form Brexit should take.
“It has failed to provide clarity about its intentions and it has been reckless about the costs of leaving without securing a deal.
“We will hold the Government to account every step of the way and fight to secure jobs and the economy, workers’ rights and environmental and consumer protection.”
Liberal Democrat leader Tim Farron accused Mrs May of rushing into negotiations “without a plan, and without a clue”.