Since 2011, United States arrears to the organization have reached about $600 million, Ms. Bokova said, but she had told members of Congress repeatedly that immediate payment was not an issue, only American political re-engagement in the organization, which she believes serves many American interests overseas.
While the Trump administration had been preparing for a likely withdrawal from UNESCO for months, the timing of the State Department's statement Thursday was unexpected.
It will establish an observer mission at the Paris-based organisation to replace its representation, the state department said.
The Israeli leader called the U.S. decision to exit UNESCO "brave and moral", according to a statement.
In July, Unesco declared the ancient and hotly contested core of Hebron, in the Israeli-occupied West Bank, as a Palestinian World Heritage site in danger, a decision sharply criticized by Israel and its allies.
"We deeply regret that the United States chose to leave UNESCO", the communique said.
In October 2016, Israel suspended its ties with UNESCO after the organization voted in favor of a resolution that warns over the escalating violence around the holy site in East Jerusalem, a territory that Israel seized in 1967 and annexed shortly later.
At the time, Netanyahu said the "absurd" vote denied the Jewish connection to the city.
UNESCO was established after World War II to help promote the free flow of information.
UNESCO is best known for its work to preserve heritage, including maintaining a list of World Heritage sites, and programmes to promote education in developing countries.
"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.
The cultural aid agency - which seeks to coordinate worldwide efforts in education, science and heritage remembrance - has been at odds with the US since 2011, when it voted overwhelmingly to offer full membership to a state of Palestine. This is a loss to the United Nations family. "This is a loss for multilateralism".
The outgoing UNESCO director-general, Irina Bokova, expressed her "profound regret" at the USA decision and tried to defend the reputation of the U.N. Educational, Scientific and Cultural Organization, best known for its World Heritage program to protect cultural sites and traditions.
It's not the first time the USA has pulled out of UNESCO: Washington did the same thing in the 1980s because it viewed the agency as mismanaged, corrupt and used to advance Soviet interests.
The U.S. rejoined UNESCO during President George W. Bush's first term.
America has made a decision to withdraw from Unesco, the United Nations programme responsible for corralling global cooperation on issues such as science and education and designating world heritage sites. But, in 1984, then-President Ronald Reagan withdrew the country from the organization, citing corruption.