Initially named the National Museum, it was built to provide the Smithsonian with its first proper facility for public display of its growing collections.

[3] The building, designed by architects Adolf Cluss and Paul Schulze, opened in 1881, hosting an inaugural ball for President James A. Garfield.

The exterior was constructed with geometric patterns of polychrome brick, and a sculpture entitled Columbia Protecting Science and Industry by sculptor Caspar Buberl was placed above the main entrance on the north side.

Pervasive complaints of dampness and the poor health of the building's occupants led to the replacement of the wood floors in the 1890s.

Balconies were added in 1896–1902 to increase space after a new Smithsonian Building failed to be authorized by the United States Congress.

"[7] Under the guidance of George Brown Goode, a historian and ichythyologist, a Division of Arts and Industries and Materia Medica was established that same year[7] and materials from the museum were sent to many late nineteenth century expositions to teach people about the country's political and natural history.

In the middle of 1975, the building was closed to the public to begin moving its remaining exhibits to the newly constructed National Air and Space Museum.

[10] In May 1976, the Arts and Industries Building reopened with 1876: A Centennial Exhibition, featuring the Philadelphia Exposition artifacts it was originally built to house.

[20] But on April 12, 2015, Smithsonian Acting Secretary Albert Horvath said about 40 percent of the building would reopen in fall 2015 for use as a short-term exhibit space.

Smithsonian officials said that the building had been architecturally stabilized, and minor refurbishments made to the bathrooms, HVAC system, and interior paint scheme.