Nancy Pelosi, a Democrat, has said that the party will block the deal in Congress if the UK’s departure from the European Union “undermines” the peace accord in Northern Ireland.
Border controls may be imposed on the island of Ireland in the event of a no-deal, which is seen as a threat to the Belfast Agreement that ended decades of bloodshed.
And the chances of the UK’s departure without a deal have been seen as increasingly likely after Boris Johnson made his “do or die” pledge to leave by the October 31 deadline.
Ms Pelosi said: “Whatever form it takes, Brexit cannot be allowed to imperil the Good Friday Agreement, including the seamless border between the Irish Republic and Northern Ireland, especially now, as the first generation born into the hope of Good Friday 21 years ago comes into adulthood. We cannot go back.
“If Brexit undermines the Good Friday accord, there will be no chance of a US-UK trade agreement passing the Congress.
“The peace of the Good Friday Agreement is treasured by the American people and will be fiercely defended on a bicameral and bipartisan basis in the United States Congress.”
If a deal is to be approved in the US it must pass both chambers of the Congress: the House of Representatives and the Senate.
The Senate is controlled by Republicans supportive of the US President, but Ms Pelosi’s party has a firm grip on the House.
His words prompted the Prime Minister to say that he expects negotiating the agreement would be a “tough old haggle” but that he remains confident that the UK “will get there”.