Senator Payne reflected on her 26 years in the federal upper house during a valedictory speech on Wednesday.
Through tears, she spoke about the plight Afghan women and girls face after the return of Taliban rule, which happened while she was in office.
"I have met some amazing Afghan women during my visits over the years and for every single one of those women their lives have been irrevocably changed for the worse," she said.
"This is unfinished business for all of us, the injustice of this treatment of women sticks in my heart and my head.
"The world must never look away, no matter where such injustices occur."
Senator Payne also spoke of the importance of keeping Australians safe, saying she was concerned the nation was losing focus on the threat of terrorism.
Acts of atrocity and "man's inhumanity to man writ large" - such as the visceral emotion she felt when visiting a former school-turned torture chamber during Cambodia's genocide - were reminders of why democratic values needed defending.
She said a failure to take action against authoritarian states was untenable "no matter what blandishments are received (or) what overtures are made".
"We must maintain an absolute focus on this threat."
Liberal frontbencher Simon Birmingham said her reflection of the women she met in Afghanistan was one of countless moments she poured her heart into as Australia's top diplomat.
"I could not have asked for a better friend, or more trustworthy confidant throughout my own Senate career," he said.
Foreign Minister Penny Wong paid tribute to her predecessor, saying her quarter-century of parliamentary service was a testament to her determination and fortitude.
"It speaks to Marise's courage and resilience that for so many years, particularly in the Howard government, she was prepared to stand her ground on issues she cared deeply about," she said.
"In doing so you demonstrated your commitment to your principals."
Senator Payne also thanked partner, former NSW minister Stuart Ayres, as well as family and colleagues who attended the speech.
She became a senator for NSW in April 1997 before becoming the first woman to be appointed Australia's defence minister in 2015 and the second woman to serve as foreign affairs minister in 2018.
She ends her career as Australia's longest-serving female senator.
Prominent 'no' campaigner against the Indigenous voice Warren Mundine and former NSW minister Andrew Constance have been touted as potential replacements for the Senate vacancy.
