Mr Tusk confirmed the momentous moment, tweeting: "After nine months the UK has delivered. #Brexit"
At the same time in the House of Commons, Ms May was telling MPs it is her “fierce determination to get the right deal for every single person in this country” as the period of negotiations begins.
The 27 EU member states and the UK will now begin an arduous process of negotiation to decide how they can disentangle their existing relations, while Ms May must push a complex legislative programme through Parliament.
Manfred Weber, an ally of the German Chancellor Angela Merkel tweeted: "EU has done everything to keep the British. From now on, only the interests of the remaining 440 million Europeans count for us. #BrexitDay"
In the Commons, the Prime Minister said Brexit was "now underway in accordance with the wishes of the British people, the United Kingdom is leaving the European Union", adding: "This is an historic a moment from which there can be no turning back."
Britain would "take control of things that matter most to us and build a stronger, fairer Britain", Ms May said. "This is our ambition and our opportunity and that is what this Government is determined to do."
Amid Conservative cheers, the Prime Minister added that triggering Article 50 was "a chance to step back and ask ourselves what kind of country we want to be".
"My answer is clear, I want the United Kingdom to emerge from this period of change stronger, more united, and more outward-looking than ever. I want us to be a secure, prosperous, tolerance country, a magnet for international talent - a country that reaches beyond the borders of Europe, too”
She acknowledged there would be “consequences” – including that Britain will “lose influence over the rules that will affect the European economy”, adding: “We accept that.”
The Prime Minister finished with a rallying cry to a divided nation, telling MPs: “This great national moment needs a great national effort. Let us come together and work together. Let us together choose to build in Britain with optimism and hope
“We can together make a success of this moment,” she insisted, by “building a Britain that our children and grandchildren are proud to call home.”
Labour leader Jeremy Corbyn said he would not give the Government a "free hand" to take the UK in the direction of a low-wage economy or tax haven for multinational firms.
"Britain is going to change as a result of leaving the European Union, the question is how. There are Conservatives who want to use Brexit to turn this country into a low-wage tax haven. Labour is determined to invest in high skill, high tech, high wage future, to rebuild and transform Britain so that no one and no community is left behind," he told the House of Commons.
"The direction the Prime Minister is threatening to take this country in is both reckless and damaging and Labour will not give this Government a free hand."
He also accused ministers of complacency and division, adding: "So far they seem utterly complacent about the scale of the task ahead: the government ministers can’t make up their minds about the real objective.
"The foreign secretary said in October that our policy is having our cake and eating it – how opposite. Today the Chancellor said the Government can’t have its cake and eat it – perhaps they should get together and talk about it."
Liberal Democrat leader Tim Farron accused Ms May of "twisting the will of the people" and said that the referendum result did not give her a mandate to leave the single market.
“The world needs liberal democratic values - this is something Churchill, Thatcher and others rightly decided that Britain could deliver from our place at the heart of Europe," he said.
“I believe the Prime Minister is twisting the will of the people, leaping into the abyss without any idea of where our country will end up. In her statement the Prime Minister admitted we would lose influence as a result.
“Theresa May has chosen the hardest and most divisive form of Brexit, choosing to take us out of the Single Market before she has even tried to negotiate. Membership of the Single Market was not on the ballot paper last June, yet without a mandate she has chosen to rip Britain, our businesses and our people out of the world’s biggest market."
More to follow...
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