Washington wants to establish permanent observer mission to UN group.
The U.S. said Thursday it has notified the UN Educational, Scientific and Cultural Organization, it would exit the group, citing "anti-Israel bias" and financial reasons.
Washington will now seek to establish a permanent observer mission to UNESCO, State Department spokeswoman Heather Nauert said in a statement.
"This decision was not taken lightly, and reflects U.S. concerns with mounting arrears at UNESCO, the need for fundamental reform in the organization, and continuing anti-Israel bias at UNESCO," Nauert said.
Arrears is a term for money that is owed.
The U.S. halted payments to UNESCO after the organization admitted Palestine as a member in 2011, but maintained a presence at the organization's headquarters in Paris.
UNESCO Director-General Irina Bokova expressed "profound regret" about Washington's action, saying in a statement that despite Washington's decision to withhold funding the U.S.-UNESCO relationship has continued to strengthen.
"At the time when the fight against violent extremism calls for renewed investment in education, in dialogue among cultures to prevent hatred, it is deeply regrettable that the United States should withdraw from the United Nations agency leading these issues," Bokova said in a statement.
"This is a loss to UNESCO. This is a loss to the United Nations family. This is a loss for multilateralism," she added.
UNESCO was formed after World War II, aimed at improving the flow of information across cultures, and is known across the globe for its World Heritage program.