She began her career in theater and later starred as Detective Deborah Saxon in the CBS daytime soap opera The Edge of Night (1976–1981).

In film, she is known for her roles in Unforgiven (1992), Titanic (1997), True Crime (1999), House of Sand and Fog (2003), Laws of Attraction (2004), The Kingdom (2007), In the Valley of Elah (2007), Jolene (2008), The Lincoln Lawyer (2011), and The Host (2013).

[5] Before she reached the age of 15, she had moved nine times and travelled because of her father's job, going to places including Italy, Turkey, Colombia, France, Canada, and Brazil.

[9] Deciding to follow her interest in theatre, she moved to New York City, where she subsequently enjoyed a 14-year stage career in regional and off-Broadway productions.

In 2015, she led the cast of My Child: Mothers of War in Los Angeles, and in 2019, she starred in the Laguna Playhouse production of The Lion in Winter with Gregory Harrison.

[10][11][12] Fisher gained recognition playing Detective Deborah Saxon on the ABC daytime soap opera The Edge of Night from 1976 to 1981.

After leaving daytime television, Fisher guest starred as a bartender, Savannah, at "The Lobo" in the first season of ABC comedy series Roseanne.

Fisher was originally cast to play Jill Taylor on the ABC sitcom Home Improvement, but was replaced after initial filming because producers felt that her pilot episode performance did not test well with the audience.

In 1991, Fisher was cast as Lucille Ball in the television film Lucy & Desi: Before the Laughter, which aired to strong ratings and good reviews.

[2] In 2005, she appeared on the ER episode "Just As I Am," as Helen Kingsley, the long-lost birth mother of Dr. Kerry Weaver, played by Laura Innes, even though Fisher is only five years older.

[13] Fisher also guest-starred on Grey's Anatomy, The Shield, Two and a Half Men, Private Practice, Sons of Anarchy, Torchwood: Miracle Day, CSI: Crime Scene Investigation, Cold Case, and Castle.

[14][15] In 2014, Fisher was starring in the ABC drama series Resurrection about the residents of Arcadia, Missouri, whose lives are upended when their loved ones return from the dead, unaged since their deaths.

[16] In 2017, she and her daughter Francesca Eastwood both starred in the acclaimed Fargo episode "The Law of Non-Contradiction" as the older and younger versions of the same character.

Her most famous role in film was as the society matron Ruth DeWitt Bukater, the mother of the character played by Kate Winslet, in the 1997 blockbuster Titanic.

[27] In the 2014 United States House of Representatives elections in California, Fisher endorsed and campaigned for Independent candidate for district 33, Marianne Williamson, an author and founder of Project Angel Food.