Gretchen Mol starred in Neil LaBute's play The Shape of Things in his original spring/summer 2001 staging at London's Almeida Theatre Company; and then in his fall/holiday 2001 staging at Manhattan's Promenade Theatre. The latter production earned her a Theatre World Award for Outstanding Debut Performance as well as a Lucille Lortel Award nomination.

Mol's film credits include Woody Allen's Sweet and Lowdown and Celebrity, Russell De Grazier's Attraction, Paul Schrader's Forever Mine, Josef Rusnak's The Thirteenth Floor, Jason Alexander's Just Looking, John Dahl's Rounders, Charlie Peters' Music from Another Room, Stephen Kay's The Last Time I Committed Suicide, Abel Ferrara's The Funeral, and Spike Lee's Girl 6 (her screen debut).

Her telefilm credits include Alfonso Arau's The Magnificent Ambersons, Ivan Passer's Picnic, HBO's Subway Stories (starring in the segment directed by Abel Ferrara), Daniel Petrie's Calm at Sunset, Calm at Dawn, and Yves Simoneau's miniseries Dead Man's Walk.

A graduate of the William Esper Studio and the American Musical and Dramatic Academy, Mol has performed in stagings of Bus Stop, An Actor's Nightmare, No Exit, Godspell and 110 in the Shade, among others.