As well as accusing UNESCO of bias, the USA state department said it was also concerned about mounting financial arrears at the agency and said it should be reformed.
The decision to withdraw from UNESCO, which the United States helped found, was announced Thursday morning by the State Department, which said the United States would remain involved as a nonmember observer.
The decision follows a string of UNESCO decisions that have drawn criticism from the USA and Israel.
Many saw the vote to include Palestine as evidence of long-running, ingrained anti-Israel bias within the United Nations, where Israel and its allies are far outnumbered by Arab countries and their supporters.
At the time, Netanyahu said the "absurd" vote denied the Jewish connection to the city.
She traced the decades-long United States ties with Unesco, and noted that the Statue of Liberty is among the many World Heritage sites protected by the United Nations agency.
May makes light of keynote speech cough with medicine-themed tweet
In a bid to rally May, audience members gave her a standing ovation while she moved away from the microphone to clear her throat. Environment Secretary Michael Gove claimed it was "a fantastic speech from a Prime Minister at the top of her game".
Washington intends to participate in the fulfillment by UNESCO of a number of its functions, including the protection of the world cultural heritage, the protection of press freedom, the promotion of scientific cooperation and the educational process.
She paid tribute to what she said had been a meaningful relationship between UNESCO and the USA, saying: "since 2011, we have deepened the partnership between the United States and UNESCO, which has never been so meaningful".
Israeli Prime Minister Benjamin Netanyahu said that Israel was preparing to pull out of UNESCO, the UN's cultural and educational agency, hours after the United States made a similar announcement.
Trump's predecessor Barack Obama slashed USA funding to the organization in 2011 after it voted to accept Palestine as a full member-state.
"At the time when conflicts continue to tear apart societies across the world, it is deeply regrettable for the United States to withdraw from the United Nations agency promoting education for peace and protecting culture under attack", she said.
The head of UNESCO, Irina Bokova, has already expressed regret over Washington's step.
The United Nation's education, cultural and scientific agency has passed several resolutions against Israel. As Foreign Policy magazine points out, the US chose to pull out of the agency in 1984 during the Reagan administration, which at that time complained of - in the words of Foreign Policy - "corruption and what it considered an ideological tilt toward the Soviet Union against the West". Under the Reagan Administration, the United States quit UNESCO in 1984, at the time accusing the agency of a pro- Soviet Union bias. It also withdrew under the Reagan administration in 1984, and rejoined in 2002 under President George W. Bush.
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