She was born Susan Abigail Tomalin in New York City to Phillip Leslie Tomalin (who had Irish, Welsh and English ancestry)[1] and Italian-born Lenora Marie Criscione. She grew up in a large family of nine children in a strict Catholic family. She was a graduate of Edison High School in 1964, and then attended The Catholic University of America from 1964 to 1968 where she attained a BA in Drama.

In 1969, Susan went to a casting call for the film Joe with her then husband Chris Sarandon; although he did not get a part, she received the major role of the disaffected teen who disappears into the seedy underworld (the film was released in 1970). Susan didn't follow up on the success of that movie, taking roles in lesser films such as Lovin' Molly; it was five more years before she appeared in The Rocky Horror Picture Show, a cult classic. That same year, she also played the female lead in The Great Waldo Pepper, opposite Robert Redford. Susan was nominated for an Oscar in 1980 for Atlantic City, but was still not a "household name" until the 1988 film Bull Durham.

Susan received four Academy Award nominations in the 1990s, finally winning in 1996 for Dead Man Walking. Her other movies include Stepmom (1998), Anywhere But Here (1999), Cradle Will Rock (1999) (portraying Mussolini's mistress), The Banger Sisters (2002), Shall We Dance (2004), Alfie (2004), Romance & Cigarettes (2005) and Elizabethtown (2005).

Susan will appear in an upcoming episode of The Simpsons as herself, which will air in spring 2006; she's appeared on the show once before as a ballet teacher. She has also made appearances on the shows Friends, Malcolm in the Middle, Mad TV, Chappelle's Show, and Rescue Me.

Susan has confirmed that she would play peace mom Cindy Sheehan in an upcoming movie.

In 1967 while in college, Susan met and married fellow student Chris Sarandon; They divorced in 1979 and she retained her married name as her stage name. In the mid-1980s, she dated actor Franco Amurri, with whom she had a daughter, actress Eva Amurri (born 1985).

Since 1988, Sarandon has been in a relationship with actor Tim Robbins, whom she met while filming Bull Durham. The couple have two children: Jack Henry (born 1989 Jack Henry Abbott) and Miles (born 1992). She and Robbins are both involved in left-wing and liberal political causes. She is also noted for always appearing in her movies dressed in off-shoulder garments.

In 2003, Susan appeared in a "Love is Love is Love" commercial, promoting the acceptance of gay, lesbian and transgendered individuals.

In 2005, Susan hosted a section of the Live 8 concert in Edinburgh, Scotland. In 2006, she participated in the 2006 Winter Olympics opening ceremony by carrying the Olympic flag in Torino.