In a pointed intervention, the Democratic Party nominee for the White House said any trade deal between the US and UK must be contingent upon respect for the agreement.
It came as Prime Minister Boris Johnson faced concerted opposition to Government moves that would override the divorce deal with Brussels regarding trade with Northern Ireland.
As Foreign Secretary Dominic Raab was visiting Washington DC to discuss the issue, former vice president Mr Biden said: "We can't allow the Good Friday Agreement that brought peace to Northern Ireland to become a casualty of Brexit.
He added: ”Any trade deal between the US and UK must be contingent upon respect for the Agreement and preventing the return of a hard border. Period."
Mr Biden's comments came as Mr Johnson saw the resignation of a senior law officer, Lord Keen, as he was forced into a compromise over controversial plans to break international law by overriding the Brexit Withdrawal Agreement (WA).
Mr Biden's remarks echoed those of Democratic Speaker of the US House of Representatives Nancy Pelosi.
Ahead of a meeting with Ms Pelosi, Mr Raab accused Brussels of the "politicisation" of Northern Ireland issues in the context of Brexit trade talks. He said the EU stance threatened the Good Friday Agreement.
Mr Raab said he had made clear the UK has an "absolute" commitment to the Good Friday Agreement.
"It is a great opportunity to be clear that the threat to the Good Friday Agreement as it is reflected in the Northern Ireland protocol comes from the EU's politicisation of the issue, and to be clear on how that has happened and why that has happened," he said following talks with US secretary of state Mike Pompeo.
"The UK action here is defensive in relation to what the EU is doing, it is precautionary, we haven't done any of this yet, and it is proportionate.
"What we cannot have is the EU seeking to erect a regulatory border down the Irish Sea between Northern Ireland and Britain, Mr Raab added.
Ms Pelosi has warned Congress would never pass a free trade agreement with the UK if legislation to override the Brexit divorce settlement was to "imperil" the peace process.
The Government will table an amendment to the UK Internal Market Bill, giving MPs a vote before it can use powers which would breach the deal brokered with Brussels last year.
Around 30 Tory rebels were thought to be preparing to vote for an amendment on Tuesday which would have required a Commons vote before the provisions in the Bill relating to Northern Ireland could come into force.
Downing Street relented and announced in a joint statement with Conservative MPs Sir Bob Neill and Damian Green that it would seek to amend the Bill to require the Commons to vote before a minister can use the "notwithstanding" powers contained within it.
The statement said: "Following constructive talks over the last few days, the Government has agreed to table an amendment for Committee Stage.
"This amendment will require the House of Commons to vote for a motion before a minister can use the 'notwithstanding' powers contained in the UK Internal Market Bill."
It came after the Government's top law officer for Scotland resigned amid reports he was unhappy about the plans to override the Withdrawal Agreement.
Lord Keen of Elie QC, the Advocate General, tendered his resignation to the Prime Minister on Wednesday morning.