There had been earlier attempts at setting up mechanics' institutes in the colony, but they struggled to find buildings which could hold their library collections and provide spaces for lectures and entertainments.

[11][12] Frederick George Waterhouse offered his services as curator of the South Australian Institute Museum in June 1859 in an honorary capacity.

[17] In 1997, championed by state Arts Minister Diana Laidlaw, the SA Museum was funded to develop its ground floor Australian Aboriginal Cultures Gallery.

Created by artists Angela and Hossein Valamanesh and commissioned by the City of Adelaide, it replaced the Lavington Bonython fountain that had occupied the site from 1965.

[20] The official role of the museum, as per the 2017/8 annual report, is: ...the conservation, study and appreciation of nature and culture for the benefit and enjoyment of current and future generations.

The Museum's exhibitions, collections, programs and science research activities contribute to global understanding of human cultures and the natural world as well as supporting life-long learning in the community.

[21]Its vision is to "...use [its] world-class collections to create and share new knowledge, focusing on Australian Aboriginal and Pacific cultures, Earth and Life Sciences".

[24] In 2011 Premier Mike Rann appointed former Adelaide Lord Mayor and Education Minister Jane Lomax-Smith as chair of the museum board.

After a public outcry as well as concern expressed by museum staff, including a protest at Parliament House in Adelaide, Premier Peter Malinauskas intervened and in late April launched a review panel to examine the plan.

[33] On 19 September 2024 Premier Peter Malinauskas announced that on the basis of the parliamentary review recommendations, the proposed restructure would not go ahead, and that a new strategic plan would be developed through collaborative consultative process.

Permanent galleries include:[40] The museum contains the most significant collection of Australian Aboriginal cultural artefacts in the world,[12] housing about 30,000 objects.

[42] In 2016, a private benefactor, Margaret Davy AM, provided funding for a new position for an Indigenous curator for five years, which she requested be named in honour of her late husband, William Geary.

[44] The museum holds the biggest collection of carvings by Arrernte artist and anthropological interpreter Erlikilyika, also known as Jim Kite, who lived at the tiny and remote European settlement at Charlotte Waters telegraph station.

[45] It also holds a bound sketchbook of 24 pencil drawings of native trees, created during the Spencer and Gillen expedition and bought by Herbert Basedow before being acquired by the Museum, as well as photographs of "Jimmy Kite" and other related materials.