NeuRA was established in 1991 as the Prince of Wales Medical Research Institute, by Professors Ian McCloskey, David Burke, Simon Gandevia and Erica Potter, with the support of the Eastern Sydney Area Health Service (now South Eastern Sydney and Illawarra Area Health Service) and the University of New South Wales.

[3] Building works began on the first phase of the project in March 2010; with the first stage of 13,000 square metres (140,000 sq ft) designed by COX Architecture completed in 2013 at a cost of A$40 million.

[5] In 2018, NeuRA formed a cooperative partnership of four clinical, educational and research allies, including Black Dog Institute, South Eastern Sydney Local Health District (SESLHD) and UNSW Sydney to create Mindgardens Neuroscience Network which became the largest collaboration between researchers and clinicians in the Southern Hemisphere on brain disorders.

In 2012, DIAN researchers showed the onset of symptoms in Alzheimer’s disease is preceded by the accumulation of amyloid (abnormal protein) in the brain over a period of 15 to 20 years.

[17] In November 2018, NeuRA’s team of neuroscientists led by George Paxinos reported a finding of a new region of the human brain which they called the endorestiform nucleus.

[18] In 2018, Professor Cyndi Shannon Weickert discovered immune cells in brains of many people with schizophrenia opening new avenues for treatment.

Also in 2019, the Sydney Brain Bank, based in NeuRA, launched a donor program in collaboration with the University of Newcastle, aimed at investigating the long-term effects of head injuries on former National Rugby League (NRL) players.

[27] Also in 2023, NeuRA's Carolyn Sue tested a new form of gene therapy aimed at slowing or stopping the progression of Parkinson’s disease.