The ancient Hill of Tara in Meath - once the seat of Ireland's high kings- has been named one of the world's 100 most endangered heritage sites.
The road will be close to the ancient monument
The World Monument Fund has placed Tara on its "crisis list" following the go-ahead for the controversial M3 motorway through the site.
The project has been bitterly opposed by environmental campaigners.
They are opposed to the route because of its proximity to the historic sites of Tara and Skryne.
Last month, work on the motorway was halted after the discovery of a highly significant archaeological find.
The World Monument Fund, based in New York, has saved 420 historical sites across the world, including the ancient Buddhist temple of Preah Khan at Angkor, Cambodia, built in 1191.
Dr Muireann Ni Bhrolchain, of the Campaign to Save Tara, said the decision to list Tara would further pressure the Irish government to rethink the motorway.
"The government ignored the 2005 statement that was signed by 350 academics from all over the world," she said.
"Perhaps at this, the 11th hour, the government in waiting will listen to the concerns of the world about the status of Tara and re-route."
Vincent Salafia of campaign group TaraWatch said: "This really is an appeal to both the Irish government and people to protect our delicate, unique heritage, which is now confirmed to be under the gravest threat."