After playing small roles in the comedies Adventures in Babysitting (1987) and Big Top Pee-wee (1988), and receiving a Tony Award nomination for her leading role in the Broadway revival of Our Town (1988–1989), Miller came to prominence with a succession of major parts in films such as The Freshman, Awakenings, Kindergarten Cop (all 1990), Other People's Money (1991), Chaplin (1992), The Shadow (1994), and The Relic (1997).

On television, Miller starred as Molly Hooper on the Fox sitcom A Minute with Stan Hooper (2003–2004), played recurring roles on Men of a Certain Age (2009–2011) and Mistresses (2013–2014), starred as Eve Carlin on the first season of ABC's American Crime (2015), and co-starred as Joyce Dahmer in the Netflix series Monster: The Jeffrey Dahmer Story (2022).

Miller graduated from high school in Los Angeles and attended Menlo College in Atherton, California for two years from 1981 to 1983, then moved to New York City to study theatre at HB Studio.

[3] Her Broadway theatre break came in 1985 when she was cast in the lead (opposite Matthew Broderick) in the Neil Simon play Biloxi Blues.

She also appeared in the 1990 movies Downtown, with Anthony Edwards and Forest Whitaker, and Kindergarten Cop, alongside Arnold Schwarzenegger, playing a teacher, hiding with her son Dominic from her criminal drug-dealing husband Cullen Crisp (Richard Tyson).

She subsequently appeared in a number of other theatrical movies, notably as Edna Purviance in Chaplin and with Tim Daly as Margaret "Maggie" Harwood in Peter Yates' film Year of the Comet, both in 1992, and the following year she appeared as the love interest of Al Pacino's character in Carlito's Way.

She appeared as Margo Lane in The Shadow with Alec Baldwin, as well as in the film Miles from Home directed by Gary Sinise.

In 2011, she portrayed Doris, the wife of protagonist George Valentin (Jean Dujardin), in the Academy Award-winning film The Artist.