The Prime Minister had pleaded with MPs of all parties to respect the vote in the referendum and back her deal.
But Labour, SNP, LibDem and many Conservative MPS rejected her pleas and it was overwhelmingly defeated by 432 votes to 202, a majority of 230.
Immediately following the vote Jeremy Corbyn announced he has tabled a no confidence vote in the Government.
The vote will take place tomorrow.
She looked to all MPs in the Commons and warned they have a responsibility to their constituents.
She said: “This is the most significant vote any of us will be part of in our careers. After all the debate, disagreement and division the time has come to make a decision that will define our country for decades to come, determine the future for our constituents, their children and grandchildren. A decision that we will have to live with and justify for years to come.”