The daughter of Canadian actor Christopher Plummer and American stage actress Tammy Grimes, Amanda Plummer grew up on the East Coast with a love of horseback riding and literature. After studying at Middlebury College and the Neighborhood Playhouse, she settled into an acting company in Massachusetts. Plummer made her film debut in the 1981 Western Cattle Annie and Little Britches opposite Burt Lancaster. Working on Broadway, she won the Tony and the Drama Desk award for her performance as Agnes in the 1982 stage production of Agnes of God. She lost the role in the film version to Meg Tilly and stayed in the theater. Some of her stage credits include The Glass Menagerie, You Never Can Tell, and A Taste of Honey. She earned another Tony nomination for her performance in Pygmalion, opposite Peter O'Toole. On television, she earned an Emmy nomination for her recurring role of mentally challenged Alice on L.A. Law.
Plummer's feature film work would consist of playing small, fragile, almost invisible characters who nevertheless leave a big impression. On the big screen, Plummer displayed her silent intensity in the non-speaking role of Ellen James in The World According to Garp (1982). She also created the interesting, if little-seen, character of Dagmar in John Patrick Shanley's Joe Versus the Volcano (1990). Her big film breakthrough came about in 1991 in Terry Gilliam's The Fisher King. She played awkward and plain office worker Lydia Sinclair, who inspires the love of a homeless man played by Robin Williams. The next year, she earned her first Emmy award for her role of concentration camp survivor Lusia Weiss in the post-war drama Miss Rose White (1992), a made-for-TV adaptation of an off-Broadway play. In feature films during the late '90s, Plummer often played slightly off-kilter women just on the verge of violent behavior. She was a disturbed sister in So I Married an Axe Murderer and an semi-balanced Castle Rock resident in Needful Things (both 1993). In 1994, she played a partner-in-crime with Tim Roth in Quentin Tarantino's Pulp Fiction. As the gun-pointing Honey Bunny, Plummer gained a lot of exposure with a minimum of screen time. The next year, she played a serial killer in Michael Winterbottom's Butterfly Kiss (1995).
Returning to television, Plummer earned another Emmy for the role of Professor Theresa Given in a 1996 episode of Showtime's The Outer Limits. For the rest of the '90s, she continued portraying delicately damaged characters in small independent films like Matthew Bright's Freeway (1996) and Peter Cohn's Drunks (1997). She also appeared in the family film A Simple Wish (1997) and lent her voice to the TV series Stories From My Childhood as well as the animated feature Hercules (1997). In 1999, Plummer revisited her earlier days as a horseback rider to play a member of the title harem in Peter Greenaway's bizarre 8 1/2 Women (1999). In 2003, she played Sarah Polley's food-obsessed co-worker in My Life Without Me. Plummer's projects for 2004 included the horror film Satan's Little Helper and Tobe Hooper's Brew.