Pursuant to Article II (6) of the UNESCO Constitution, U.S. withdrawal will take effect on December 31, 2018.
"This is a loss for multilateralism", said UNESCO Director-General Irina Bokova in a statement.
The US has a long history of contradictions with UNESCO, an global body that is aimed at promoting a respect for the rule of law and human rights through cultural and scientific collaboration.
The United States said Thursday that it was pulling out of the UN's culture and education body, accusing it of "anti-Israel bias" in a move criticised by the head of the Paris-based organisation.
Until that time, the United States, which provides around $80 million to UNESCO annually, will remain a full member.
UNESCO was once a low-profile United Nations agency best known for producing a list of World Heritage sites such as the Grand Canyon or Cambodia's Angkor Wat, as well as running science, media and cultural programmes internationally.
Israel has also announced today that they will be quitting the United Nations agency, and Israeli Prime Minister Benjamin Netanyahu called the decision by the U.S. "brave and moral".
The US helped found Unesco in the wake of the Second World War, with the aim of ensuring peace through the free flow of ideas and education. Israel would pull out on the same date as the U.S.
UNESCO is responsible for coordinating worldwide cooperation in education, science, culture and communication.
In recent years, Israel has repeatedly complained about what it says is the body taking sides in disputes over cultural heritage sites in Jerusalem and the Palestinian territories.
In a statement released via her official Twitter handle, Bokova called the withdrawal "a loss to UNESCO".
Israel, meanwhile, remains a member of UNESCO.
"This is another example of the Trump's administration's profound ambivalence and concern about the way the U.N.is structured and behaves, and it shows the administration's determination to separate itself from its predecessors", said Aaron David Miller, a former Middle East negotiator and adviser in Republican and Democratic administrations.
In July, the agency again delighted Palestinians when its members declared the Old City of Hebron in the occupied West Bank an endangered World Heritage site - described as "another delusional decision" by Israeli Prime Minister Benjamin Netanyahu.
But according to Nikki Haley, the US ambassador to the United Nations, the Trump administration found it to be a step too far when the agency decided this summer to designate "the Old City of Hebron and the Tomb of the Patriarchs as part of Palestinian territory".
Its head, Irina Bokova, earlier called the USA withdrawal a matter of "profound regret".