Giving official notice under Article 50 of the Lisbon Treaty, it will be delivered to European Council president, Donald Tusk later.
In a statement in the Commons, the prime minister will then tell MPs this marks “the moment for the country to come together.”
It follows June’s referendum which resulted in a vote to leave the EU.
The BBC reports that Mrs. May’s letter will be delivered at 12:20 BST on Wednesday by the British ambassador to the EU, Sir Tim Barrow.
The prime minister, who chaired an hour long cabinet meeting earlier, is set to make a statement to MPs confirming the countdown to the UK’s departure from the EU is under way.
She will promise to “represent every person in the whole United Kingdom” during the negotiations – including EU nationals, whose status after Brexit has yet to be settled.
“It is my fierce determination to get the right deal for every single person in this country,” she will say.
“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.”