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Dubois was born in Brooklyn, New York. Among her other credits, she appeared in the 1969 made–for–TV holiday film J.T.; Love of Life between 1970–72 as Loretta Allen. In 1970, Dubois played the role of a quarrelsome laundress alongside Carrie Snodgrass in the cult classic "Diary of a Mad Housewife". She has appeared on several shows as a guest star, including a 1972 role on Sanford and Son, as Fred's old flame Juanita.
Her appearance in a play of Hot l Baltimore at Mark Taper Forum got her noticed by Norman Lear, and led to her being cast in Good Times and in films. Dubois was often cast as characters older than her true age; when Good Times premiered in 1974, Dubois was 28, just two years older than Jimmie Walker. The character of Willona was supposed to be close in age to that portrayed by Esther Rolle, who was 53 at the time. According to most sources, Rolle enjoyed working with Dubois, despite the age difference. After John Amos was fired from the show, with his character James Evans being killed off, Rolle disagreed with the show's new direction, and left the show herself. Her departure made Dubois the de facto star of the series, alongside Walker.
Dubois has three children; Rani (former actress), Yovanne and Burghadt Dubois. In 1996, Dubois was one of the attendees of Adrienne Lois Brown, James Brown's wife's, funeral. Like her late mentor Esther Rolle, Dubois is a member of Zeta Phi Beta sorority. In 2000, in her hometown of Amityville, New York, she was honored as the grand marshal for the North Amityville Community Parade and Festival Day.