Now work starts to ensure best outcome for Wales
The Prime Minister has triggered Article 50 after her letter to European Council President Donald Tusk was delivered by Ambassador Sir Tim Barrow in Brussels.
Mr Tusk immediately responded on Twitter: "After nine months the UK has delivered. #Brexit."
Kicking off the two-year process of withdrawal from the European Union, Theresa May told MPs: "This is a historic moment from which there can be no turning back.
"Now is the time for us to come together, to be united across this House and across this country to ensure that we work for the best possible deal for the UK and the best possible future for us all."
Wales First Minister Carwyn Jones (below) said: "Today signals the end of months of speculation and the start of a critical period of negotiation which will shape our future relationship with Europe and the wider world.
"We remain committed to the priorities set out in our white paper, Securing Wales' Future, which puts full and unfettered access to the Single Market first and foremost.
"Our white paper sets out a sensible negotiating position for the UK as a whole, and has already influenced the UK Government's approach in important areas including maintaining full access to the Single Market, upholding existing employment rights and the importance of transitional arrangements.
"While we have often been frustrated with the processes by which we've arrived at this point today, we must now concentrate on the job in hand. We stand ready to work constructively with the UK Government to secure a deal which protects Welsh businesses, our economy and the future prosperity of Wales.
"If, as negotiations progress, we believe our priorities are not being championed or our representation falls below a level we find acceptable, we will not remain silent. We will not allow Wales to be side-lined - we will be outspoken and our voice will be heard.
"As a leader of a country which voted to leave the EU, we are wholly focused on securing Wales' future. We will step up to the plate and do all we can to deliver the best possible outcome for Wales."
Leader of the Welsh Conservatives, Andrew RT Davies (below left), said: "Today is a historic day for Wales and the United Kingdom as the Prime Minister and Conservative Government delivers on the will of the people.
"As we move forward during the negotiation process we will ensure all voices are represented and this significant moment represents an opportunity for the country to come together and heal any divisions which appeared during the referendum.
"We have been steadfast in our determination to secure the right deal for communities across the country and to ensure we embrace the opportunities that lie ahead as one united nation.
"As a country we are stronger as one and as a party we believe Wales and the United Kingdom can prosper outside the European Union; a view which to date has sadly not been shared by other political parties.
"It is vital Labour's First Minister now engages positively in this process - not simply shouting from the side-lines - something which he spectacularly failed to do so yesterday when stooping to new lows in a political desire to scaremonger communities across the country.
"For the nationalists such as Plaid Cymru - the question for them is one of relevance. They purport to be the Party of Wales but have been anything but since June 23rd and pushing an independence agenda which threatens our economy and the existence of our public services in Wales is simply not the answer.
"The momentous journey begins in earnest today; and the Prime Minister has our full support as she negotiates on behalf of the people of Wales. A negotiation which sets out to deliver a global nation that builds relationships with old friends and new allies around the globe."
The Chair of the Welsh Assembly's External Affairs and Additional Legislation Committee, David Rees AM, said: "The triggering of Article 50 marks a significant moment in the history of our country.
"The two-year negotiating period will now begin in earnest and our cross-party committee will work tirelessly to ensure that the Welsh voice is heard in London, in Brussels, and in capitals across Europe.
"Irrespective of party, or of where we stood during the referendum, we must now come together in the Welsh interest.
"We have years of hard work ahead of us and we will need to draw on the expertise and talents of the Welsh people to get a deal that is right for Wales."
Plaid Cymru's Brexit spokesperson, and Wales' member of the Brexit Select Committee, Jonathan Edwards, said: "The British Government has made a choice to pursue the most extreme Brexit option possible and the weak and divided Labour opposition has allowed it to happen.
"It doesn't have to be this way. There is a better way - a sensible and moderate Brexit, protecting our economic links with the rest of the world and our place within the Single Market, protecting the funding from which so many across Wales and the rest of the British Isles benefit and protecting the opportunities for young people to expand their horizons and career prospects.
"The Prime Minister said that she would seek a UK-wide agreement before beginning her Brexit negotiations but instead she has acted as if she is the head of a unitary British State, wilfully ignoring the fact that she is the Prime Minister of a Union of four members. The weak and divided Labour opposition has allowed this to happen and the spineless Labour Welsh Government continues to neglect its duty to stand up to Westminster for the interests of the people of Wales.
"The UK Prime Minister has set the British State on a course towards a cliff-edge but it doesn't have to be this way. Plaid Cymru will continue to fight for a more sensible conclusion to the Brexit referendum that puts jobs, wages and people's quality of life before irresponsible ideological obsessions."
The Assembly's presiding officer Elin Jones said: "Today, the UK Government has formally triggered the process to take us out of the European Union.
"Leaving the EU brings complex challenges and opportunities for us in Wales and for the public policy areas for which the Assembly has responsibility.
"In last year's Referendum, leaving the EU was the will of the majority of the people whom we serve in the Assembly.
"We have a critical role in ensuring that the voice of the Welsh people is properly heard in the negotiations ahead of us.
"Assembly Committees are already undertaking important work in setting out our expectations of the Welsh and UK Governments and addressing the questions that need to be answered.
"My priorities are to ensure that the Assembly plays a full part in overseeing these negotiations and scrutinises effectively the Great Repeal Bill and the huge volume of further legislation that will follow.
"We are entering a period when fundamental changes will be made to the constitutional arrangements of the UK, the place of the devolved nations within it, and the ability of the Assembly to deliver for the people of Wales.
"As that process unfolds, I am determined to demonstrate and secure the Assembly's role as a strong, effective Parliament for Wales.
Leader of the Welsh Liberal Democrats Mark Williams said: "Theresa May has chosen the hardest and most divisive form of Brexit.
"She has chosen to force her own interpretation of the referendum outcome on Wales and the United Kingdom, tearing Wales' businesses, farmers, and industry out of the world's biggest single market.
"I welcome the commitment to the transfer of powers to Wales, however Wales must have the resources to effectively deliver for the people of Wales on those new powers.
"The Liberal Democrats will continue to fight for the people of the UK to have the last say on the final Brexit deal. Democracy didn't end on 23rd of June - and it hasn't ended today either."