Boris Johnson has been warned that the US Congress would block a free trade deal with the UK if he rips up his Brexit agreement.
US House Speaker Nancy Pelosi blasted the "deeply concerning" plans to "unilaterally discard" the Northern Ireland Protocol, a key part of the Prime Minister's Brexit deal.
She made it clear that attempts to press ahead with the move could endanger a UK-US trade deal.
In a strongly-worded statement, Ms Pelosi said: "It is deeply concerning that the United Kingdom is now seeking to unilaterally discard the Northern Ireland Protocol.
"Negotiated agreements like the Protocol preserve the important progress and stability forged by the Good Friday Accords, which continue to enjoy strong bipartisan and bicameral support in the United States Congress.
"As I have stated in my conversations with the Prime Minister, the Foreign Secretary and Members of the House of Commons, if the United Kingdom chooses to undermine the Good Friday Accords, the Congress cannot and will not support a bilateral free trade agreement with the United Kingdom."
Her comments are a reminder of the keen interest in Northern Ireland from senior figures in Washington as tensions escalate at Stormont over post-Brexit trading rules
It comes after Foreign Secretary Liz Truss confirmed this week that she would bring forward legislation to unilaterally override post-Brexit trade rules for Northern Ireland.
The UK wants the power to change border rules - without the EU's permission - to ease disruption for businesses and resolve a mounting political crisis at Stormont.
The DUP has refused to join the devolved government in Northern Ireland in protest over the creation of a trade border in the Irish Sea.
Power-sharing between unionists and nationalists is a fundamental part of the Good Friday Agreement, which is enshrines the peace process in Northern Ireland.
But changing the Northern Ireland Protocol would infuriate Brussels, sparking fears over a potential trade war with the EU.
The Prime Minister's spokesman said: "We welcome that the US shares our deep commitment to the Belfast Good Friday Agreement and the peace process and has urged the EU to show flexibility.
"You heard Liz Truss earlier this week how protecting the hard-won gains of the Belfast Good Friday Agreement is our priority, which is why we want to reach a negotiated settlement with the EU."
The spokesman said it was "not about scrapping the protocol" but "fixing the serious issues that parts of it are causing".
Taoiseach Micheal Martin accused the UK Government of moving the goalposts after holding talks with party leaders in Belfast on Friday.
"This was a deal that the UK Government signed up to, ratified in their parliament and they are now unhappy with aspects of it," he said.
"Well, let's try to resolve those aspects in a meaningful way and that means getting into the tunnel and negotiate in a serious way."
He said the Northern Ireland Assembly must be formed while talks are ongoing.
DUP leader Sir Jeffrey Donaldson hit back at Ms Pelosi, insisting that it was "absolutely evident" that the Good Friday Agreement was already being undermined.
After speaking to the Irish premier, he said: "We spelled it out very clearly to him the problems with the protocol, the harm it is doing to Northern Ireland and that we need a solution, we need decisive action to deal with these problems.
"We are not interested in a sticking plaster approach, or tinkering around the edges, it has to be fundamental change which respects Northern Ireland's place within the UK internal market and nothing short of that will suffice."