UNESCO and its mandate for international cooperation can be traced back to a League of Nations resolution on 21 September 1921, to elect a Commission to study feasibility.
 On 18 December 1925, the
International Bureau of Education (IBE) began work as a
non-governmental organization in the service of international educational development. However, the onset of
World War II largely interrupted the work of these predecessor organizations.
After the signing of the
Atlantic Charter and the
Declaration of the United Nations, the Conference of Allied Ministers of Education (CAME) began meetings in London which continued between 16 November 1942 to 5 December 1945. On 30 October 1943, the necessity for an international organization was expressed in the Moscow Declaration, agreed upon by China, the United Kingdom, the United States and the USSR. This was followed by the
Dumbarton Oaks Conference proposals of 9 October 1944. Upon the proposal of CAME and in accordance with the recommendations of the
United Nations Conference on International Organization (UNCIO), held in San Francisco in April–June 1945, a United Nations Conference for the establishment of an educational and cultural organization (ECO/CONF) was convened in London 1–16 November 1945 with 44 governments represented. A prominent figure in the initiative for UNESCO was
Rab Butler, the
Minister of Education for the United Kingdom.
 At the ECO/CONF, the Constitution of UNESCO was introduced and signed by 37 countries, and a Preparatory Commission was established.
 The Preparatory Commission operated between 16 November 1945, and 4 November 1946—the date when UNESCO's Constitution came into force with the deposit of the twentieth ratification by a member state.
The first General Conference took place between 19 November to 10 December 1946, and elected Dr.
Julian Huxley to Director-General.
 The Constitution was amended in November 1954 when the General Conference resolved that members of the Executive Board would be representatives of the governments of the States of which they are nationals and would not, as before, act in their personal capacity.
 This change in governance distinguished UNESCO from its predecessor, the CICI, in how member states would work together in the organization's fields of competence. As member states worked together over time to realize UNESCO's mandate, political and historical factors have shaped the organization's operations in particular during the Cold War, the decolonization process, and the dissolution of the USSR.
Among the major achievements of the organization is its work against racism, for example through influential
statements on race starting with a declaration of anthropologists (among them was
Claude Lévi-Strauss) and other scientists in 1950
 and concluding with the 1978
Declaration on Race and Racial Prejudice.
 In 1956, the Republic of South Africa withdrew from UNESCO claiming that some of the organization's publications amounted to "interference" in the country's "racial problems."
 South Africa rejoined the organization in 1994 under the leadership of
UNESCO's early work in the field of education included the pilot project on fundamental education in the Marbial Valley, Haiti, started in 1947.
 This project was followed by expert missions to other countries, including, for example, a mission to Afghanistan in 1949.
 In 1948, UNESCO recommended that Member States should make free primary education compulsory and universal.
 In 1990, the World Conference on Education for All, in
Jomtien, Thailand, launched a global movement to provide basic education for all children, youths and adults.
 Ten years later, the 2000
World Education Forum held in
Dakar, Senegal, led member governments to commit to achieving basic education for all by 2015.
UNESCO's early activities in culture included, for example, the Nubia Campaign, launched in 1960.
 The purpose of the campaign was to move the
Great Temple of Abu Simbel to keep it from being swamped by the Nile after construction of the
Aswan Dam. During the 20-year campaign, 22 monuments and architectural complexes were relocated. This was the first and largest in a series of campaigns including
Borobudur (Indonesia) and the
Acropolis (Greece). The organization's work on heritage led to the adoption, in 1972, of the Convention concerning the Protection of the World Cultural and Natural Heritage.
World Heritage Committee was established in 1976 and the first sites inscribed on the
World Heritage List in 1978.
 Since then important legal instruments on cultural heritage and diversity have been adopted by UNESCO member states in 2003 (Convention for the Safeguarding of the
Intangible Cultural Heritage
) and 2005 (
Convention on the Protection and Promotion of the Diversity of Cultural Expressions
An intergovernmental meeting of UNESCO in Paris in December 1951 led to the creation of the European Council for Nuclear Research, which was responsible for establishing the
European Organization for Nuclear Research (CERN)
 in 1954.
Arid Zone programming, 1948–1966, is another example of an early major UNESCO project in the field of natural sciences.
 In 1968, UNESCO organized the first intergovernmental conference aimed at reconciling the environment and development, a problem which continues to be addressed in the field of sustainable development. The main outcome of the 1968 conference was the creation of UNESCO's
Man and the Biosphere Programme.
In the field of communication, the "free flow of ideas by word and image" has been in UNESCO's constitution from its beginnings, following the experience of the Second World War when control of information was a factor in indoctrinating populations for aggression.
 In the years immediately following World War II, efforts were concentrated on reconstruction and on the identification of needs for means of mass communication around the world. UNESCO started organizing training and education for journalists in the 1950s.
 In response to calls for a "
New World Information and Communication Order" in the late 1970s, UNESCO established the International Commission for the Study of Communication Problems,
 which produced the 1980
MacBride report (named after the Chair of the Commission, the Nobel Peace Prize laureate
 The same year, UNESCO created the
International Programme for the Development of Communication (IPDC), a multilateral forum designed to promote media development in developing countries.
 In 1991, UNESCO's General Conference endorsed the
Windhoek Declaration on media independence and pluralism, which led the UN General Assembly to declare the date of its adoption, 3 May, as
World Press Freedom Day.
 Since 1997, UNESCO has awarded the
UNESCO / Guillermo Cano World Press Freedom Prize every 3 May. In the lead up to the
World Summit on the Information Society in 2003 (
Geneva) and 2005 (
Tunis), UNESCO introduced the
Information for All Programme.
 Laws passed in the United States in 1990 and 1994 mean that it cannot contribute financially to any UN organisation that accepts Palestine as a full member.
 As a result, it withdrew its funding which accounted for about 22% of UNESCO's budget.
 Israel also reacted to Palestine's admittance to UNESCO by freezing Israel payments to the UNESCO and imposing sanctions to the
 claiming that Palestine's admittance would be detrimental "to potential peace talks".
 Two years after they stopped paying their dues to UNESCO, US and Israel lost UNESCO voting rights in 2013 without losing the right to be elected; thus, the US was elected as a member of the Executive Board for the period 2016–19.