Quinlan made her film debut in George Lucas' 1973 nostalgic look at the early '60s, American Graffiti at the age of 19 (although she did appear in an uncredited role in 1972's One is a Lonely Number). As a young actress, she guest-starred in several 1970s television series, including Police Woman, Ironside, Emergency!, Kojak, and The Waltons.
She has appeared in over 50 films but is perhaps best known for her roles as Deborah, a schizophrenic, in the film version of I Never Promised You a Rose Garden, for which she earned a Golden Globe nomination for Best Actress in a Motion Picture-Drama, and for a Golden Globe and Oscar-nominated turn in the Best Supporting Actress category as an astronaut's wife, Marilyn Lovell, in the 1995 true story Apollo 13 opposite Tom Hanks.
Quinlan also made a mark as Jim Morrison's Celtic pagan lover Patricia Kennealy in Oliver Stone's The Doors and won a Blockbuster Entertainment Award as Favorite Supporting Actress-Suspense, for Breakdown with Kurt Russell. Her recent work includes the TV series House, the 2006 remake of the horror classic The Hills Have Eyes, the wife of a government traitor in the 2007 film Breach, the mother of the brothers in the Fox drama Prison Break, and a senator in a 2011 episode "Alliances" of the science-fiction series Stargate Universe. Another notable credit is her role as Peters in the sci-fi-fi horror film Event Horizon.