The National Museum of the Philippines traces its history to the establishment of the Museo-Biblioteca de Filipinas during the Spanish colonial period, by virtue of a royal decree of the Queen-Regent of Spain, Maria Cristina, that was approved at the recommendation of the Overseas Minister of the Spanish Government, Victor Balaguer, on August 12, 1887.  Sebastián Vidal y Soler, inspector-general of forests in the Philippines and director of the Botanical Garden in Manila, served as the first (acting) director of the Museo-Biblioteca. He was followed by fellow Spaniards Julián Romero, chief forester, in 1890, and Tomás Torres, director of the School of Arts and Trades, in 1893. 

The Museo-Biblioteca opened to the public on October 24, 1891 at the Casa de la Moneda on Cabildo Street in Intramuros, then home of the Philippine Mint, later moving to Gunao Street in Quiapo. In 1894, the first Filipino director of the Museo-Biblioteca, Pedro A. Paterno, was appointed, and he served until the institution became inactive in 1900 in the early years of the American occupation of the Philippines. 

The museum functions of the Museo-Biblioteca were reestablished as the Insular Museum of Ethnology, Natural History and Commerce which was created by the Philippine Commission, led by Civil Governor William H. Taft, on October 29, 1901, under the Department of Public Instruction. David Barrows was the officer-in-charge. One of the reasons for the creation of the Insular Museum was to complement the Bureau of Non-Christian Tribes, and it was later, in 1903, integrated with the Bureau of Ethnological Survey under the Department of the Interior, with anthropologist Alfred Jenks as officer-in-charge.

In 1905, after the Louisiana Purchase Centennial Exposition at St. Louis, Missouri that was held in the previous year, the name of the Insular Museum was changed to the Philippine Museum, with anthropologist Merton Miller as superintendent. At the same time, the Bureau of Ethnological Survey became the Division of Ethnology under the Department of Public Instruction in 1905 and then under the Bureau of Science, which housed considerable natural history collections, in 1906. 

A decade later, in 1916, the Fine Arts Division of the Philippine Museum was merged with the Philippine Library (precursor of the National Library and National Archives) to create the Philippine Library and Museum under the Department of Justice, and this was led by a succession of distinguished Filipino scholars: Teodoro M. Kalaw, Macario Adriatico, Enrique Filamor, José C. Zurbito, Trinidad H. Pardo de Tavera, and Epifanio de los Santos. The Natural History Division and Division of Ethnology were maintained in the Bureau of Science.

In 1928, the National Museum of the Philippine Islands was created and placed under the Department of Agriculture and Natural Resources, with Manuel de Yriarte y Alveyra appointed as director. It was housed in two buildings: the Ayuntamiento building in Intramuros for the collections of the Division of History and Fine Arts, and the Supply Building in the Port Area behind the Manila Hotel for the collections of the Ethnology and Anthropology Divisions, which included archaeology, ethnography and physical anthropology. The natural science collections were not included in the organization as they were part of the Bureau of Science on Herran, now Pedro Gil Street. The National Library of the Philippine Islands was also established as a separate institution. Yriarte died in office and succeeding him as directors in acting capacity between 1930 and 1932 were geologist Leopoldo Faustino, chemist Angel Argüelles, and Jorge Vargas. 

In 1932, another reorganization took place when the Division of Fine Arts was transferred to the National Library, and the Division of Ethnology and the Division of Anthropology were combined with the sections of natural history of the Bureau of Science and organized into the National Museum Division of the Bureau of Science under Leopoldo Faustino, who was followed in 1934 by botanist Eduardo Quisumbing. In 1939, the National Museum Division was renamed the Natural History Museum Division of the Bureau of Science under the office of the Secretary of Agriculture and Commerce.

During the Battle for Manila in February 1945, virtually the entire national collections were destroyed when the Legislative Building, where most items were placed for safekeeping, as well as the Bureau of Science building, were reduced to ruins. 

After the war, under the newly independent Philippine Republic, the Natural History Museum Division was reunited with the National Library’s Fine Arts Division to become the National Museum under the Office of the Executive Secretary, by virtue of Executive Order No. 94 issued by President Manuel Roxas, with Eduardo Quisumbing appointed as director.

In 1951, the National Museum was placed by President Elpidio Quirino under the Department of Education as one of its bureaus. In 1962, President Diosdado Macapagal appointed Galo Ocampo as director, and he was followed, under President Ferdinand E. Marcos, by Gemma Cruz in 1969, zoologist Godofredo L. Alcasid in 1971 and, in acting capacity, archaeologist Alfredo E. Evangelista in 1979. 

Regulatory functions were added to the National Museum, starting in 1966 with the passage of Republic Act No. 4846, which provided for the protection and preservation of Philippine cultural properties, and continuing through the 1970s, including management of important cultural sites around the country. In addition, the National Planetarium in Rizal Park was established under the National Museum in 1975. During this time, the National Museum was housed in one floor of the Legislative Building, as well as in the reconstructed building of the National Science Development Board, formerly the Bureau of Science, in Ermita, Manila. 

Following landmark studies in the field of archaeology and anthropology, as well as the celebration of various historical milestones, the first component regional and site museums of the National Museum were developed starting in the 1960s and expanded rapidly in succeeding decades. The establishment of the National Historical Institute in 1972 also led to the transfer of personnel from what was the Art and History Division of the National Museum as well diverse historical collections. 

In 1987, anthropologist Fr. Gabriel S. Casal was appointed director by President Corazon Aquino. 

In 1996, President Fidel V. Ramos established a presidential committee to oversee the creation of a National Museum complex. Earlier in 1994, he had instructed the Secretaries of Finance and Tourism to prepare for the eventual transfer of their neo-classical buildings in Rizal Park to the National Museum, and in 1995, the Finance Building was turned over. The Department of Tourism was scheduled to transfer custody of the Tourism building by the end of 1997, but this initiative was delayed. In a historic move, the Senate of the Philippines also vacated its chambers in the Executive House, as the Legislative Building was then called, to allow for the landmark building to be incorporated into the National Museum precinct.

On February 12, 1998, Republic Act No. 8492, The National Museum Act of 1998, was approved by President Ramos as the charter of the National Museum that detached it as bureau of the Department of Education and reestablished the institution as an autonomous government trust instrumentality under a Board of Trustees, and which designated the President of the Philippines as the Honorary Chairman and Patron of the National Museum. Later that year, the first stage of the National Museum complex was realized with the formal inauguration of the Museum of the Filipino People in the converted Old Finance Building, a key part of official commemoration of the centennial of Philippine independence that culminated on June 12, 1998. 

In 1999, Antonio O. Cojuangco, Jr. was appointed as the first chairperson of the Board of Trustees by President Joseph Ejercito Estrada, and anthropologist Corazon S. Alvina became director in 2001.

Hilarion M. Henares, Jr., was appointed as chairperson by President Gloria Macapagal Arroyo in 2010, followed by Ramon del Rosario, Jr., appointed by President Benigno S. Aquino III later that same year. Jeremy Barns became director, also in 2010.

The vision for the National Museum Complex in Manila as formulated in the 1990s was revived with the turnover of the Tourism Building in 2013 to allow for the establishment of the National Museum of Natural History, which opened on May 18, 2018. Later that year, Luli Arroyo Bernas was appointed Chairperson by President Rodrigo Roa Duterte.

At the same time as the inauguration of the National Museum of Natural History in 2018, the Museum of the Filipino People would be renamed as the National Museum of Anthropology and the National Art Gallery, inaugurated as such in 2001 at the Old Legislative Building, would likewise be renamed as the National Museum of Fine Arts, thus presenting a complete complex of central museums.

On April 26, 2019, Republic Act No. 11333, the National Museum of the Philippines Act, was approved by President Duterte, replacing the earlier charter of the institution. The law was enacted to update the mandate of the institution in the management and development of museums and collections of national significance in the fields of arts, cultural heritage, and natural history, and to enable it to be more responsive to prevailing needs, expectations and conditions. Its organization was expanded and headed by a director-general.

In 2022, President Ferdinand R. Marcos, Jr., appointed Andoni Aboitiz as Chairperson of the Board of Trustees.

Among many things, the new charter of the National Museum provides for deeper regionalization of management and operations to allow the National Museum to better serve the entire national community, which is especially reflected in new component museums inaugurated in Cebu City in 2023 and Davao City in 2024.