She starred in the 2002 Broadway revival of Into the Woods, for which she received a Drama Desk Award nomination.
In 1998 she received Joseph Jefferson Award nomination for Best Actress in a Principal Role in a Musical for Elmer Gantry at the Marriott Theatre in Chicago, Illinois.
On television, O'Malley made guest-starring appearances on Law & Order, Law & Order: Special Victims Unit, NYPD Blue, The King of Queens, My Name Is Earl, Monk, Criminal Minds, The Mentalist, Hart of Dixie, Masters of Sex and Grey's Anatomy.
She had recurring roles on Brotherhood, Boardwalk Empire, Shameless, Strange Angel, Snowpiercer and Why Women Kill.
[8] In 2023, O'Malley starred in the action thriller film The Killer directed by David Fincher, receiving positive reviews for her performance.