Millender-McDonald was born in Birmingham, Alabama. She was educated at Los Angeles Harbor College; at the University of Redlands, from which she received a business degree; and at California State University, Los Angeles, from which she earned a masters in educational administration; and the University of Southern California, from which she completed her doctorate in public administration. She worked as a teacher, a textbook editor, and later as director of a nonprofit organization working for gender issues. She was a member of Alpha Kappa Alpha sorority. Millender-McDonald served as a member of the City Council of Carson, California and was a member of the California State Assembly (after beating two sitting incumbent Democrats that had been reapportioned into the same Carson based assembly district in 1992) before entering the House. She was first elected to the House in a March 1996 special election to replace Congressman Walter Tucker, who resigned due to corruption charges and was later sentenced to 27 months in prison. While she won a difficult nine-candidate primary in her first election run (fellow assembly member Willard Murray came in a close second) she did not face any serious opposition in any of her reelection campaigns.