Her father John was an agent with the William Morris Agency who represented Leo Carrillo, Loretta Young, Ed Wynn, and Carole Lombard.

[3] Through her father's connections, Tyrrell was employed in the theatrical production of Time Out for Ginger (1963) starring Art Carney in New York City.

[3] 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 (play) at The American Place Theatre.

In 1992, she guest starred on an episode of Wings "Marriage Italian Style" and she performed her own one-woman show, Susan Tyrrell: My Rotten Life, a Bitter Operetta.

[3] 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).

Tyrrell moved to New York City in the early 1960s to focus on theater work, for the first time meeting and socializing with openly LGBT people.

The artistic crowd of "New York freaks" she associated with included "Andy Warhol people", among them Candy Darling, with whom Tyrrell had a relationship and shared an apartment.

[6] In the mid-1970s, Tyrrell had a two-year relationship with actor Hervé Villechaize and shared a home with him in the Laurel Canyon area of Los Angeles.