She will be present at the event to kick off the UN body's general conference, which will be held at the UN Educational, Scientific and Cultural Organisation's headquarters in Paris. Heads of state and government ministers from many of the 190 countries that are now UNESCO members will also attend, a statement from the organisation said.
President Bush marked the return of his country to the organisation in an address to the United Nations on 12 September 2002, saying, "This organisation has been reformed and America will participate fully in its mission to advance human rights, tolerance and learning."
That speech was intended to enlist UN support for the proposed invasion of Iraq. Now, shortly after his most recent appeal to the UN for support in Iraq, his pledge is about to take effect.
The United States, under president Ronald Reagan, withdrew from UNESCO in 1984 to protest what it saw as financial mismanagement and anti-US bias in some policies.
President Bill Clinton nudged his country back towards the UNESCO fold after judging that the organisation had changed, and US lawmakers in May agreed to unblock some $60 million (55 million euros) in back dues for membership to formally resume on 1 October.
Britain, which followed the US departure with its own in 1985, rejoined UNESCO in 1997.
Laura Bush's trip to Paris to see the US flag raised with those of other member countries will be only her second abroad as first lady. She accompanied her husband on his Africa tour in July.
UNESCO's original slogan reflected its founding principles, "Since wars begin in the minds of men, it is in the minds of men that the defences of peace must first be constructed." UNESCO describes its mission as building those defences of peace "by promoting collaboration among nations through education, science, culture and communication."
This "one world" approach continues to rankle with some American conservatives, who accuse UNESCO of attempting to infringe upon US sovereignty.
The UN body's general conference which follows the opening ceremony will run to 17 October and will be attended by five heads of state - presidents Jacques Chirac of France, Carlo Azeglio of Italy, Askar Akayev of Kyrgyzstan, Alejandro Toledo of Peru and Gloria Arroyo of the Philippines - and more than 300 ministers.
Its main points of business include examining draft texts on protecting intangible cultural heritage such as languages, culture in times of war and occupation, and artistic works held in digital media like the Internet.