The Government has slumped to a 10th defeat over flagship Brexit legislation in the Lords as peers backed a move aimed at preventing a hard border being imposed between Northern Ireland and the Republic.
Voting was 309 to 242 - majority 67 - for a cross-party amendment to the Brexit Bill enshrining support for the Good Friday peace agreement and continued north-south cooperation.
It came as the Prime Minister held crunch talks with senior ministers over post-Brexit customs arrangements.
Former Tory Cabinet minister Lord Patten of Barnes warned against going back to the "old animosities" and "old feuds" in Northern Ireland post-Brexit.
Lord Patten said it would be "shameful and dishonourable" and a "stain on our history" if the Lords did anything to make that more likely.
Introducing the successful amendment, Lord Patten said his aim was to support the Prime Minister by largely re-stating government policy while some Tory MPs were keen to tip the country "over the cliffs onto the rocks" and make life difficult for Mrs May. Recalling the years of violence which left thousands dead and many others maimed during the Troubles, he said: "We cannot possibly want to risk going back to that."
Lord Patten turned on those who had warned the Lords was "playing with fire" by amending the Bill, saying: "I'll tell you what I think playing with fire is.
"It's blundering into the politics of Northern Ireland with a policy which is sometimes clueless and sometimes delinquent - with a can of petrol and a box of matches in the other hand. I don't want to go back to the old humiliations, the old animosities, the old feuds."
But there was criticism of the move from senior Northern Ireland politicians, including Tory peer and former Stormont first minister Lord Trimble, who argued that Brexit would not damage the Good Friday agreement, but the amendment would "because it excludes the people of Northern Ireland".
He said links between Belfast and Dublin had been good, but the behaviour of the Taoiseach, supported by the European Union, was "actually destroying that relationship and doing considerable damage to it".
Lord Carswell, a former Lord Chief Justice in Northern Ireland and independent cross-bencher, said Brexit would not mean "some sort of iron curtain". Highlighting the "real hard border" during the Troubles, including armed checkpoints and watch towers, he said: "There is no suggestion whatever, and should never be, that we want to return to that or will do so."
Lord Eames, the former Archbishop of Armagh and Primate of All Ireland, warned ministers that the border issue was "extremely dangerous". He told peers that there was a growing apprehension in Northern Ireland that "we will be left to carry the can".
The independent cross-bench peer said: "There's a lot more hanging on this debate this afternoon than simply the question of what we do with security and arrangements on the border.
"What is at stake is the reversal, or the danger of the reversal, of all that has been achieved. The peace process is still an infant growing."
Northern Ireland Minister Lord Duncan of Springbank insisted the EU's chief negotiator, Michel Barnier, had to listen to both communities in Northern Ireland.
If Mr Barnier failed to hear the people of Northern Ireland "then he will be derelict in his responsibilities", Lord Duncan added. He vowed the Government's support for the Good Friday agreement was "unwavering and steadfast".