The letter is to be hand-delivered to EU President Donald Tusk in Brussels on Wednesday, formally triggering the process to end Britain's 44-year membership in the bloc.
From then, there are exactly two years to settle the terms of the divorce before it comes into effect in March 2019.
Around the same time the letter is delivered, May will address the British parliament and vow to achieve a Brexit deal for everyone in the UK, including EU nationals - of which there are around three million in the UK. The divisive campaign ahead of the June 2016 vote, and aftermath of the result, have left many EU citizens in Britain worried about their future.
UK Parliament clears way for Brexit
01:03
This browser does not support the video element.
"It is my fierce determination to get the right deal for every single person in this country," May will say, according to comments released in advanced by her office.
"We are one great union of people and nations with a proud history and a bright future. And, now that the decision has been made to leave the EU, it is time to come together," she will say.
May has a tough job ahead of her - negotiating with the EU's 27 other member states on issues like finance, trade and security, while dealing with semi-autonomous Scotland's renewed push for independence.
The push is seen as protest at Brexit - Scotland voted overwhelmingly to remain in the European Union, as did Northern Ireland, which is currently in a political crisis and risks losing self-government. Scottish and Northern Irish voters were outnumbered by support for Brexit in England and Wales.
Brexit: What lies ahead?
Britain has triggered EU Article 50, formally starting the process for the country to leave the 28-nation bloc. DW takes a look at some of the steps involved and the time required to strike an exit deal.
Image: Getty Images/J. Taylor
What is Article 50?
Article 50 of the Treaty of Lisbon gives any existing member of the European Union the right to quit unilaterally and outlines the procedure for doing so. It gives the state concerned two years to negotiate a deal for its exit. Once Article 50 is triggered, it cannot be stopped, except by the unanimous consent of all member states.
Image: Reuters/T. Melville
What does Article 50 actually say?
There are five elements in Article 50. They state that the exiting country must notify the European Council formally and that it is given a two-year period to reach an agreement. Article 50 also states that the country concerned cannot take part in EU’s internal discussions about its departure. The exit deal must be approved by a "qualified majority" and must also get the backing of MEPs.
Image: picture alliance/dpa
When will it be triggered?
The UK decided in favor of leaving the EU in a referendum in June 2016. After lengthy parliamentary debates and legal procedures, Prime Minister Theresa May looks all set to send a formal letter of notification to EU President Donald Tusk on March 29, which will trigger Article 50. Officials in Brussels have already outlined a divorce bill for Britain of between 55 and 60 billion euros.
Image: Reuters/Y. Herman
What happens after that?
The EU is expected to give a first response later this week. A summit of EU leaders on April 29 is then to lay down guidelines for the Brexit talks, which are expected to start in May or June. The hardest part of the negotiations will be determining the status of more than a million Britons living in other parts of the EU and of some 3 million EU citizens in Britain, and working out trade details.
Image: picture alliance/dpa/A. Vitvitsky/Sputnik
The Great Repeal Bill
By autumn this year, the UK government is expected to introduce legislation to leave the EU and put all existing EU laws into British law - the Great Repeal Bill. The possible move will annul the 1972 European Communities Act (ECA), which gives EU law instant effect in the UK, and give parliament the power to absorb parts of EU legislation into UK law, scrapping elements it does not want to keep.
Image: picture-alliance/empics/PA
How long will the process last?
EU leaders have said they want to conclude the talks within 18 months to allow the terms of the exit to be ratified by UK and the European Parliaments as well as the EU states. If no agreement is reached in two years and no extension is agreed, the UK automatically leaves the EU and all existing agreements.
Image: picture-alliance/dpa/A. Rain
What if the UK changes its mind?
The fifth paragraph of Article 50 raises the possibility of a state wanting to rejoin the EU after having left it. This would be considered under Article 49.
