Senator Dodson, a respected Indigenous leader who represents Western Australia, said his recent cancer treatment meant his health had left him physically unable to fulfil his parliamentary duties.
"This morning I informed the Labor Party parliamentary caucus of my intention to resign as senator for Western Australia, with effect from January 26, 2024," he said in a statement on Tuesday.
He thanked Prime Minister Anthony Albanese for appointing him as special envoy for reconciliation and to lead the implementation of the Uluru Statement from the Heart.
A Yawuru man from Broome, Senator Dodson has dedicated his life to building mutual respect between Indigenous and non-Indigenous Australians.
Prior to his endorsement by Labor as a WA senator in March 2016, he was a member of the Australian National University Council, Adjunct Professor at the University of Notre Dame and co-chair of the National Referendum Council.
He was a commissioner in the landmark royal commission into Aboriginal deaths in custody.
Mr Albanese described him as a "wonderful Australian and an excellent human being".
"From the moment he entered parliament, he has made this place a better one," the prime minister said."As a boy, he hid in the long grass while the police and welfare officers took his mates."Yet despite what must have been such a traumatic experience as a child, he grew into the Father of Reconciliation - a figure of grace, dignity and inspiration."