Opened on 27 May 1881, the Museum was built to house a large collection of objects obtained from around the world by Dr. Schomburgk, the then Director of the Adelaide Botanic Garden, which some are still on display today.

The Museum is listed on the Register of the National Estate, 1980; Register of State Heritage Items, 1982; classified by the National Trust; and on the Register of City of Adelaide Heritage Items, 1985.

Grieve Gillett Architects was commissioned as the conservation architect to restore the interior of the Museum to its former glory. The Museum was reopened to the public in May 2009 after the display cases were fitted out and the historical collection was restored. The second stage of the project involved restoration of the building exterior.