The US is pulling out of the United Nation's Education, Scientific and Cultural Organisation (UNESCO) accusing it of having an anti-Israel bias.
The agency is known for designating such as Syria's Palmyra and the US Grand Canyon as world heritage sites.
The state department said it would establish an observer mission at the Paris-based organisation to replace its representation.
Unesco head Irina Bokova said the withdrawal was a matter of profound regret.
In 2011, the US cancelled its budget contribution to UNESCO in protest at its decision to grant full membership to the Palestinians.
Foreign Policy magazine reported that the US withdrawal is also motivated by a desire to save money.