The US was angered in 2011 when UNESCO members granted Palestine full membership of the body, despite opposition from its ally Israel.
"This is a loss for multilateralism", said UNESCO Director-General Irina Bokova in a statement.
The Trump administration and Israel have voiced concern over a series of Unesco decisions, including the listing of the city of Hebron as a Palestinian world heritage site. In addition to anti-Israel bias, the department cited "the need for fundamental reform" and "mounting arrears" at the organization.
The US stopped paying dues to the global body in late 2011 after the agency voted to accept a Palestinian bid for full membership and now owes approximately $550 million, a State Department spokesperson said.
"This truth has become even more evident today, at a time when the growth of extremism and terrorism calls for new long-term solutions for peace and freedom, in the context of combating racism and anti-Semitism, in combating ignorance and discrimination", she said.
One of UNESCO's founding nations, the United States has had a rocky relationship with the Paris-based organization over the years.
"This decision was not taken lightly", according to a State Department statement on Thursday.
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The organization has a long history of taking anti-Israel measures, and supporting resolutions against the Jewish state. Permanent Representative to the UN Nikki Haley has repeatedly denounced these actions, and said the US was "evaluating" whether or not it should continue as a member of the organization. The officials, who were not authorized to be publicly named discussing the issue, said the USA was notably angry over UNESCO resolutions denying Jewish connections to holy sites and references to Israel as an occupying power.
Nauert also clarified that, in accordance with the charter of UNESCO, the decision on "the USA withdrawal will enter into force on December 31, 2018".
The third round saw the breakthrough of French candidate Audrey Azouley, who secured 18 out of 58 votes of the UNESCO Executive Board, sharing top spot with Qatari candidate Hammad bin Al-Kawari.
In 2011 the USA cut its funding to the agency - slashing its budget by 22 percent - in protest at its decision to grant full membership to the Palestine.
The resolution also criticised Israel's activities at holy places in Jerusalem and the occupied West Bank. It referred to the holy site only using Muslim names and prompted angry reactions from Israeli politicians.
Israeli Prime Minister Benjamin Netanyahu called the vote "another delusional decision" by UNESCO, which promotes education, cultural development and free media initiatives around the world.
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