It was established in April 1987 to replace the former Australian Atomic Energy Commission (AAEC), which was founded in 1952.

Its headquarters and main research facilities are on the southern outskirts of Sydney in Lucas Heights, Sutherland Shire.

The Australian Nuclear Science and Technology Organisation Act 1987 (Cth) prescribes its general purpose.

A third, smaller unit, being a 100 kW thermal Argonaut-class reactor named MOATA, was in operation between 1961 and 1995, before being decommissioned in 2009.

Spent fuel from the reactors is transported to Port Kembla, then shipped to France for reprocessing.