It is named after Sir Henry Ayers, five times Premier of South Australia and wealthy industrialist, who occupied it from 1855 until 1897.

Plans for the two-storey mansion, which for the greater part of its existence was named Austral House,[1] were developed in 1846 for William Paxton, an Adelaide chemist.

Internally, the rooms feature hand-painted ceilings, stencilled woodwork and memorabilia from the Ayers family, demonstrating the wealth of the owners at the time it was built.

[citation needed] The names given to many of the rooms, and their functions, were revealed in notes made by Sir Henry when he recorded the temperatures in various places in the house during Adelaide's very hot weather.

Restoration work was undertaking by a team of Artlab Australia specialists, who "resecured each individual paint flake by applying a consolidant".

[citation needed] The Government of South Australia bought the property in 1926 for nurse accommodation and training – it was opposite the now-closed Adelaide Hospital.

[citation needed] In the 1960s, the National Trust of South Australia campaigned successfully to save the building from demolition since it was "the last of the grand mansions of Adelaide's North Terrace boulevard".

[9] Mindful of its tourism potential, he instigated its renovation as a tourist and cultural centre that included a museum and fine-dining and bistro restaurants.

[11] Costumes, silverware, artworks, furniture, a 300-kilogram (660 lb) chandelier and the original gasoliers were displayed in the museum area.