Harris created numerous TV series: Soap, Benson, The Golden Girls, Empty Nest, Nurses, and The Golden Palace. She also wrote or co-wrote all of the episodes of Soap and appeared on two episodes of that show as a hooker named Babette. Her most successful show was The Golden Girls. Harris married television producer Paul Junger Witt on September 18, 1983; he co-produced all the shows she created. She was married from 1965 to 1969 to the late actor Berkeley Harris.
The first script Harris sold was Then Came Bronson. She then wrote for Love, American Style, All in the Family, The Partridge Family and the TV adaptation of Neil Simon's Barefoot in the Park. Her abortion episode for the Bea Arthur-starring series Maude in the 1970s won Harris the Humanitas Prize. She would later work with Arthur again in the 1980s when Arthur took one of the lead roles in The Golden Girls.
Harris has chronic fatigue syndrome, which affected her ability to participate in the production of The Golden Girls. In an episode of that show entitled "Sick and Tired" (1989), Harris wrote some of her struggles into the storyline where Arthur's character Dorothy was diagnosed with chronic fatigue syndrome.
Harris formed the production company Witt/Thomas/Harris with Paul Junger Witt and Tony Thomas. She was honored with the Writers' Guild's Paddy Chayefsky Award in 2005 and inducted into the Television Academy Hall of Fame in 2011.
Harris' husband, Paul Junger Witt, died in April 2017 following a battle with cancer.