Susan Tyrrell made her Broadway debut in 1965 as a replacement performer in the comedy Cactus Flower. In 1968, as a member of the Repertory Theatre of Lincoln Center, she was in the cast of King Lear and revivals of The Time of Your Life (1969) and Camino Real (1970). Off-Broadway, Tyrrell appeared in the 1967 premiere of Lanford Wilson’s The Rimers of Eldritch and a 1979 production of Father’s Day at The American Place Theatre. Tyrrell’s television debut was in Mr. Novak (1964) and her film debut was in Shoot Out (1971). Tyrrell was nominated for an Academy Award for Best Supporting Actress for her performance as Oma in John Huston’s Fat City (1972). In 1978, the actress won the Saturn Award for Best Supporting Actress for her performance in Bad (1977). Later, Susan Tyrrell starred as Queen Doris in the indie Forbidden Zone (1980). She sang the film’s song, “Witch’s Egg”. A year later, she portrayed Vera in Tales of Ordinary Madness (1981). From 1981 to 1982, Tyrrell starred as Gretchen Feester, in the ABC’s short-lived situation comedy series Open All Night. She then had a starring role in the exploitation horror film Night Warning. Other appearances included roles in Tales of Ordinary Madness (1981) and Night Warning (1982).

In 1985 Susan Tyrrell played Solly, in the sexploitation film Angel and its sequel, Avenging Angel. Then followed roles in the adventure film Flesh+Blood, the Vincent Price anthology horror film From a Whisper to a Scream (1987), the animated feature film The Chipmunk Adventure (1987), and Big Top Pee-wee (the 1988 sequel to 1985’s Pee-wee’s Big Adventure) followed. Tyrrell took a supporting role in John Waters’ Cry-Baby (1990). In 1992, Tyrrell performed her own one-woman show, Susan Tyrrell: My Rotten Life, a Bitter Operetta. In the late 1990s, Tyrrell had roles in the Tales from the Crypt episode, “Comes the Dawn” (1995); the animated series Extreme Ghostbusters (1997); and the psychological thriller film Buddy Boy (1999). In the 200s, Susan Tyrrell appeared in Bob Dylan’s Masked and Anonymous (2003), and The Devil’s Due at Midnight (2004). Her final appearance was in the 2012 independent film Kid-Thing. In 2008, the actress moved to Austin, Texas, to be closer to her niece and died there on June 16, 2012. In January 2012, Tyrrell wrote in her journal, “I demand my death be joyful and I never return again.” Following her death, she was cremated and her ashes scattered.