Joe Biden said on Tuesday night that he did not want to see a guarded border in Ireland.
The US president-elect said he had discussed the matter with Boris Johnson and other European leaders.
Asked what his message to Brexit negotiators was, Mr Biden said: "We do not want a guarded border. We want to make sure. We’ve worked too long to get Ireland worked out.
"And I talked with the British prime minister, I talked with the Taoiseach, I talked with others, I talked to the French.
"The idea of having a border north and south once again being closed is just not right, we’ve just got to keep the border open."
Mr Johnson put forward legislation in September that would break the Northern Ireland protocol of the Brexit divorce treaty that seeks to avoid a physical customs border between the British province and EU-member Ireland.
Mr Biden was speaking in Delaware shortly after he announced nominees to his cabinet.
The president-elect, who is proud of his Irish heritage, said he was "always happy" to take a question about Ireland.
In September he issued a warning that the Good Friday Agreement must not be a "casualty of Brexit" and made clear a UK-US trade deal would be dependent on that.
He said any trade deal between the US and UK would be contingent upon there being no "return of a hard border. Period."
Mr Biden discussed Brexit with Mr Johnson earlier in November during one of his first phone calls to other world leaders as president-elect, warning him Brexit must not jeopardise the Northern Ireland peace process.
Negotiations between the UK and European Union on a post-Brexit trade deal resumed on Monday following technical discussions over the weekend.
Problematic issues including fishing rights, the "level playing field" aimed at preventing unfair competition in areas such as workers' rights and state subsidies and the governance of any deal are yet to be resolved.