Announcing the appointment on Friday, Attorney-General Mark Dreyfus was confident Justice Mortimer would significantly contribute to the justice system.
"She is widely recognised for her intellectual capacity and judicial leadership," he said.
Justice Mortimer will be the fifth chief justice of the Federal Court appointed since the court was established in 1976.
She has been involved with many groundbreaking cases in the areas of migration, the environment and anti-discrimination.
In 2016, Justice Mortimer ruled the Queensland Police Service unlawfully discriminated in relation to the 2004 death of an Aboriginal Palm Island resident in custody.
She also presided over the native title agreement granted to Kaurna elders in Adelaide in 2018 - the first positive determination of native title over a capital city after the Native Title Act came into force.
Justice Mortimer has received a number of awards for her work, including the Australian Human Rights Commission Law Award and the 2011 Law Council of Australia President's Medal.
Recently, Justice Mortimer heard the workplace dispute between political activist Sally Rugg and independent MP Monique Ryan.
She will begin her appointment on April 7, having served the Federal Court since 2013.
Justice Mortimer has also been a member of the Victorian Bar and was made Senior Counsel in 2003.
Mr Dreyfus thanked retiring Chief Justice James Allsop who was head of the court since 2013.
Asked whether more women will be appointed to senior roles, Mr Dreyfus said they would do so on merit.
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