Theresa May has officially triggered Article 50 today, launching two years of negotiations that will end with Brexit in 2019.
The letter informing the European Council of Britain's intention to leave the European Union has been handed to European Commission president Donald Tusk in Brussels.
Speaking to MPs in the House of Commons the Prime Minister described it as an "historic moment from which there can be no turning back".
In her six-page letter, May said she hoped for a "deep and special partnership" between the EU and Britain.
She said the Government would like an early agreement on a transitional period and accepted there will be "consequences" from Brexit.
May warned the EU that negotiations on the terms of Britain's "divorce bill" must take place alongside talks on a new trade deal the remaining member states.
German Chancellor Angela Merkel has already rejected May's call for parallel talks on Brexit divorce and a future trade deal.
She said talks on British divorce terms will come first then, "hopefully soon", on the UK-EU's future relationship.
May has also warned that failure to come to a Brexit agreement could see a weakening of security cooperation.
Tusk said to Britain: "We already miss you. Thank you and goodbye".
The 27 other members of the European Union have vowed to "act as one and preserve its interests" in Brexit talks with the UK.
But they have warned Britain might not be fully out of the European Union until 2022.
EU politicians are also demanding that the European Court of Justice will "settle any legal challenges" over the process of leaving the EU.
The MEPs also made clear that there should be no "trade-off between internal and external security including defence cooperation, on the one hand, and the future economic relationship on the other hand".
EU parliamentary negotiator Guy Verhofstadt said rights of EU citizens must be the first priority now Britain has triggered Article 50.
He said: "For us that is an absolute priority and the parliament thinks, in fact, it should be the first subject in the negotiations.
"They should not be bargaining chips."