Chalfant was born Kathleen Ann Bishop[1] in San Francisco, California, and was raised in her parents' boarding house in Oakland.

She earned the Outer Circle Critics, Drama Desk, Obie and Lucille Lortel awards for her performance as Vivian Bearing in Margaret Edson's Pulitzer Prize-winning play Wit in 1998; she shaved her head for the role.

Chalfant has played recurring roles in a number of television series including House of Cards, Law & Order, Rescue Me, and The Guardian.

[13] In 2018, Chalfant read T. S. Eliot's Four Quartets at the Bard SummerScape Festival as part of a new performance with choreography by Pam Tanowitz, music by Kaija Saariaho, and images by Brice Marden.

They have a son, David Chalfant, who was the bass player for the folk-rock band The Nields, and a daughter, Andromache, a set designer in New York.