LaDuke is the daughter of an Anishinabeg (Ojibwe) ("Chippewa") father and Jewish mother who worked as an art professor. She was raised on the west coast of the United States, but after graduating from Harvard in 1982 with a degree in native economic development, she accepted a job as principal of the high school of the White Earth Ojibwe reservation in Minnesota. She soon became an activist, involved in the struggle to recover lands promised to the Ojibwe by a 1867 treaty. She helped the Ojibwe buy back thousands of acres of ancestral land.
LaDuke was named Woman of the Year by Ms. Magazine in 1997 and won the Reebok Human Rights Award in 1998. She is the founder of the White Earth Land Recovery Project in Minnesota, the Indigenous Women's Network, and the Honor the Earth Fund.
LaDuke is the author of the novel, Last Standing Woman, and the non-fiction book, All our Relations: Native Struggles for Land and Life.
LaDuke is the mother of three.