Dee joined the American Negro Theater as an apprentice, working with Sidney Poitier, Harry Belafonte, and Hilda Simms. She made several appearances on Broadway, such as her first role in ANT's 1946 production of Anna Lucasta. Her first onscreen role was in That Man of Mine in 1946. She received national recognition for her role in the 1950 film The Jackie Robinson Story. In 1965, Dee performed in lead roles at the American Shakespeare Festival as Kate in The Taming of the Shrew and Cordelia in King Lear, becoming the first black actress to portray a lead role in the festival. Her career in acting crossed all major forms of media over a span of eight decades, including the films A Raisin in the Sun, in which she recreated her stage role as a suffering housewife in the projects, and Edge of the City. She played both roles opposite Poitier.