The foundation of the gallery's collection was a donation of approximately 1,000 works owned by Arthur M. Sackler, a New York City psychiatrist who also contributed $4 million toward the construction of the building. The Sackler Gallery was opened in 1987 and, along with the Freer Gallery (Freer Gallery of Art), houses the Smithsonian Institution's Asian art. The Sackler features extensive collections of Chinese jade figures, dating from Neolithic times to the 19th century, and bronze (bronze work) sculpture from the Shang (Shang dynasty) through Han (Han dynasty) dynasties. It also contains a collection of 19th- and 20th-century Japanese art (arts, East Asian), and the Vever Collection of Persian and Indian manuscripts, books, and paintings. It includes as well artworks from rural India, contemporary Chinese ceramics, and paintings from China (including Tibet), Japan, India, and Korea. The gallery frequently displays international exhibitions on loan from other museums. The Sackler publishes the journal Artibus Asiae in cooperation with the Rietberg Museum in Zürich and sponsors scholarly lectures and symposia on specialized topics in Asian art. It shares a research library with the Freer Gallery.

In 1999 the gallery significantly expanded its collection when Paul Singer, another psychiatrist and art collector, donated an additional 5,000 Chinese works to the museum.