The pointed intervention by the Democratic Party nominee for the White House came as Prime Minister Boris Johnson faces 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, who is leading incumbent president Donald Trump in a slew of nationwide polls ahead of the November election, insisted a future trade deal between the US and UK could only happen if the peace agreement was respected.
Mr Biden tweeted on Wednesday: “We can’t allow the Good Friday Agreement that brought peace to Northern Ireland to become a casualty of Brexit.
“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.”
Health Secretary Matt Hancock appeared unconcerned about the presidential candidate's remarks, saying he has "every confidence" that the UK and the US will strike a deal.
"I saw the remarks that Joe Biden made, and he said that the most important thing is to protect peace on the island of Ireland and that is right at the top of our priority list too," he said.
The government has come under fire from the EU over the UK Internal Market Bill which would allow ministers to override parts of the Brexit Withdrawal Agreement regarding trade with Northern Ireland.
The PM 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).
The Foreign Secretary said the UK had “absolute” commitment to the Good Friday Agreement and accused Brussels of the “politicisation” of Northern Ireland issues in the context of Brexit trade talks.
Mr Raab said he had had “very positive discussions” with Republicans and Democrats.
“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’s comments came after the speaker of the US House of Representatives, Nancy Pelosi, 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.