Commencing operation on 1 January 2015, it was responsible for the state's health system, as well as various other aspects of social policy.

The DHHS was formed following machinery of government changes in the aftermath of the 2014 state election, assuming the functions of the previous Department of Health and Department of Human Services, respectively.

On 30 November 2020, the Premier announced that Health and Human Services functions would be separated into a new Department of Health (DoH) and the Department of Families, Fairness and Housing (DFFH).

The new DoH would oversee public health, aging, mental health and ambulance service portfolios while DFFH would hold responsibility for child protection, housing and disability.

As part of this change, DFFH would gain a number of functions that currently reside with The Department of Premier and Cabinet.