After graduating from the University of Alberta (BEd 1974), Blondin-Andrew taught school at several Northwest Territories communities during 1974-81 before joining the territorial department of education at Yellowknife as a language specialist during 1981-84. There she became involved in policy development for the preservation of Indigenous languages and culture in the Northwest Territories.
During 1984-86 she was successively manager and then acting director of the Public Service Commission of Canada, and during 1986-88 she was assistant deputy minister of culture and communications at Yellowknife. In the 1988 general election, she became the first Indigenous woman elected to Parliament when she won the Western Arctic seat for the Liberals, serving as Opposition critic for Aboriginal Affairs (now Indigenous and Northern Affairs Canada). She was re-elected in 1993, as the Liberals came to power, and was appointed Secretary of State, Training and Youth that year.