Elizabeth Ann Perkins was born on November 18, 1960, in Queens, New York, and raised in Vermont. Her mother, Jo Williams, was a concert pianist and drug treatment counselor, and her father, James Perkins, was a businessman, farmer, and writer. Perkins is of Greek and English descent.
She studied acting at Chicago's Goodman School of Drama at DePaul University for three years before launching her professional career with a co-starring gig in the touring company of Neil Simon's Brighton Beach Memoirs in 1986. She made her Broadway debut as a replacement in the same play in the spring of 1984.
As a stage actress, Perkins has worked with Playwrights Horizon, the Ensemble Studio, The New York Shakespeare Festival, and the Steppenwolf Theater in Chicago. She was listed as one of the 12 "Promising New Actors of 1986" in John Willis' Screen World.
Perkins made her film debut in 1986 in Edward Zwick's About Last Night... and had a career breakthrough co-starring with Tom Hanks in Big. She received critical acclaim for her performance in Barry Levinson's Avalon and was a standout opposite William Hurt in The Doctor.
She has since appeared in a wide range of films, including Miracle on 34th Street, 28 Days, The Ring Two, Indian Summer, Moonlight and Valentino, Crazy in Alabama, Jiminy Glick in Lalawood, The Flintstones, The Thing About My Folks, He Said, She Said, Must Love Dogs, and Finding Nemo.
Perkins has also had a successful television career, starring in the Showtime series Weeds from 2005 to 2009 and earning two Golden Globe nominations for her performance. She has also appeared in a number of other television projects, including My Sisters Keeper, If These Walls Could Talk, Rescuers: Stories of Courage: Two Women, How to Live with Your Parents, GLOW, From The Earth to the Moon, Sharp Objects, Truth Be Told, Curb Your Enthusiasm, and The Moodys.
She is currently starring in Season 2 of The Moodys and plays the role of Mandy Moore's mother on the hit series This Is Us.