Moore moved to New York City in 1983, working as a waitress before being cast in the dual roles of Frannie Hughes and Sabrina Hughes on the soap opera As the World Turns, for which she won a Daytime Emmy Award; she played the roles from 1985 to 1988. In 1987 she was part of the junior company in the New York premiere of Caryl Churchill's Serous Money at the Public Theater. Because of Screen Actors Guild rules, she had to change her name, since there were already actresses named "Julie Smith" and "Julianne Smith". She chose her father's middle name, "Moore", but because there was already another actress named "Julie Moore", she finally settled on "Julianne Moore."

Moore began starring in feature films in the early 1990s, mostly appearing in supporting roles in films like The Hand That Rocks the Cradle, Benny and Joon, and The Fugitive. Her part in 1993's Short Cuts gained her critical acclaim and recognition, and she was cast in several high-profile Hollywood films, including 1