Linda Burney, the Minister for Indigenous Australians and first Aboriginal woman in the lower house, will retire from politics at the next election.
Skills and Training Minister Brendan O'Connor, who also sits in cabinet, will join Ms Burney to retire at the end of this term of government.
The pair will step down from their positions as ministers immediately, prompting a ministry refresh.
Announcing their retirements, Prime Minister Anthony Albanese said he was proud to call Ms Burney and Mr O'Connor his friends.
"I am proud to have witnessed first-hand their passion for this nation, their determination to leave this country better," he said.
Labor will call for nominations to its frontbench, and Mr Albanese expects to announce his new ministry on Sunday, when they will be sworn in.
Ms Burney has represented the Sydney seat of Barton since 2016, when she became the first Indigenous woman elected to the House of Representatives, and later the first Indigenous woman to serve as Indigenous Australians minister.
Hopefully the ABC will follow the BBC in setting up accounts in the Fediverse