Nine months after the divisive Brexit referendum last June, the Prime Minister will officially trigger Article 50 in a letter that will be hand delivered in Brussels.
At the same time, in a statement to MPs in the Commons, she will pledge to get the right deal for everyone in the UK, including EU nationals living in this country.
"We are one great union of people and nations with a proud history and a bright future," she will say.
"And, now that the decision has been made to leave the EU, it is time to come together."
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While the Prime Minister's approach on the historic day of the triggering of Article 50 will be typically business-like, many Brexit-supporting Conservative MPs are in a mood to celebrate.
Although Tory MPs have been discouraged from holding Article 50 parties, many are preparing to defy the plea and begin celebrating immediately after the PM has finished answering questions on her statement.
There is also a mood of anticipation and excitement in Whitehall. One senior Government source, describing the mood ahead of triggering Article 50, said: "It's like Christmas Eve".
The letter invoking Article 50, signed personally by the PM, will be delivered to European Council president Donald Tusk by Britain's EU ambassador Sir Tim Barrow at around 12.30pm UK time.
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At the same moment in the Commons - and immediately after the regular weekly PMQs - Mrs May will rise to set out her ambitions for Brexit, having earlier briefed senior ministers at a Cabinet meeting at 8am.
In her Commons statement, she will say: "When I sit around the negotiating table in the months ahead, I will represent every person in the whole United Kingdom - young and old, rich and poor, city, town, country and all the villages and hamlets in between."
And, significantly, after strong pressure from MPs in recent months, she will add: "And yes, those EU nationals who have made this country their home."
On the Brexit negotiations, which will now get under way and could last two years, she will pledge: "It is my fierce determination to get the right deal for every single person in this country.
"For, as we face the opportunities ahead of us on this momentous journey, our shared values, interests and ambitions can - and must - bring us together.
"We all want to see a Britain that is stronger than it is today. We all want a country that is fairer so that everyone has the chance to succeed.
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"We all want a nation that is safe and secure for our children and grandchildren. We all want to live in a truly global Britain that gets out and builds relationships with old friends and new allies around the world.
"These are the ambitions of this Government's Plan for Britain. Ambitions that unite us, so that we are no longer defined by the vote we cast, but by our determination to make a success of the result."
Labour leader Jeremy Corbyn, who will respond to the PM's statement, said ahead of the triggering of Article 50 that his party would hold the Government to account all the way.
"The Conservatives want to use Brexit to turn our country into a low wage tax haven," he claimed.
"Labour is determined to ensure we can rebuild and transform Britain, so no one and no community is left behind.
"It will be a national failure of historic proportions if the Prime Minister comes back from Brussels without having secured protection for jobs and living standards.
"That's why Labour has set the clear priorities of full access to the European market, rights at work and environmental protection. And we will hold the Government to account every step of the way."
UKIP leader Paul Nuttall claimed his party would be "the guard dogs of Brexit, holding the Government's feet to the fire" and he warned there must be "no backsliding".
"Today the Government will finally act on the historic decision of the people of this country to leave the European Union," he said. "Finally, nine months after our vote, the UK will formally inform the EU that we are leaving.
"UKIP is delighted that this is eventually happening. Twenty-four years ago this party was formed to make this a reality, so it would be churlish to complain.
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"We have been ignored, dismissed insulted and abused, but through determination and with good humour we fought on and we have succeeded."
But Mr Nuttall claimed: "The nine months' delay has, of course, cost the taxpayer additional billions, and has allowed those who would block the democratic will of the people to do all they can to spread discord, but we are here now.
"While negotiations continue we will continue to be the 'guard dogs of Brexit', holding the Government's feet to the fire at home and our MEPs will be working to ensure our friends on the continent do not pull any fast ones.
"We will provide the political threat to ensure no backsliding takes place and ensure that Brexit does indeed mean 'Exit'.
"But today, for now, we wish the Government and the Prime Minister well.
"If they fail in this historic task, 17 million people are ready to act."
