From South Carolina, MacDowell dropped out of Winthrop College to become an Elite model. Her name was Rose MacDowell, but the agency reinvented her as Andie. In her early twenties, she lived in Paris. Calvin Klein commercials led to her being cast in Greystoke (1984), and with Sex, Lies, and Videotape (1989) she arrived as a Hollywood leading lady.
MacDowell has three children by her first marriage, to Paul Qualley, Justin (1986), Rainey (1989) and Sarah (1995). She next married Rhett Hartzog, a jeweller she had known at school, and thirdly Kevin Geagan, a car dealer. She was chosen by People magazine as one of the Fifty Most Beautiful People in the World and also has an honorary doctorate from Lander University.