Health Department boss Martin Bowles will exit the role next week after staff were told the veteran public servant would retire following a 40-year career.
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Mr Bowles, who took the helm at the department in 2014, will finish on September 1 ending a career spanning multiple departments.
Before heading up the Health Department, he led the Department of Immigration and Border Protection, and was deputy secretary at the Department of Climate Change and Energy.
He also worked at the Defence Department, where recently he was tipped as a contender to succeed Dennis Richardson as secretary before Greg Moriarty, former chief-of-staff to Prime Minister Malcolm Turnbull, was appointed.
Mr Bowles was a public servant for the Queensland and New South Wales governments before joining the Australian Public Service in 2006 to be Defence's deputy secretary.
He moved in 2010 to the Department of Climate Change and Energy Efficiency, where his work on energy efficiency policies and remediating the disastrous home insulation program was awarded the Public Service Medal two years later.
Health Minister Greg Hunt said Mr Bowles had a distinguished public service career and had driven change at the Health Department.
Prime Minister Malcolm Turnbull said the public servant had built a well-deserved reputation as a highly respected leader and driver of innovation.
Health Department deputy secretary Mark Cormack will be acting secretary while a successor for Mr Bowles is found.
Mr Bowles is the second departmental boss to announce his departure in one month, after Department of Environment and Energy secretary Gordon de Brouwer said he would quit next month "to pursue other interests".