The daughter of a Michigan factory worker, McMillan earned a BA in journalism at Berkeley, but dropped out of Columbia's screenwriting program, partly due to her struggles with addictions. Eventually, she became an associate professor at the University of Arizona and published her first novel, "Mama" (1987) which McMillan had to promote herself. Her second novel, "Disappearing Acts" was a bestseller in 1989, and she found even greater success when "Waiting to Exhale" was published three years later. When the screen rights to this story of four female friends (one is divorcing her husband, one is divorced from a gay man, and all are looking for love) were sold, 20th Century-Fox allocated a mere $14 million to the production not expecting it to have "crossover" appeal. Directed by Forest Whitaker and starring Whitney Houston, Angela Basset, Loretta Devine and Lela Rochon, the film was a surprise hit, grossing more than $65 million domestically.
The success of the film put McMillan in demand: her script for "Disappearing Acts", which focused on the relationship between a singer and a construction worker, was originally announced as a feature at MGM but the rights were later acquired by Wesley Snipes' Amen Ra Productions which expects to film the story as an HBO movie. In 1996, her novel "How Stella Got Her Groove Back", which focused on the relationship between a woman and a much younger man whom she meets on a Jamaican holiday, became an instant best-seller with the screen rights snapped up by Fox. Again in tandem with Ron Bass, McMillan served as an executive producer and screenwriter on the film which starred Angela Bassett, Whoopi Goldberg and newcomer Taye Diggs.