Susanna Thompson was born on January 27, 1958 in San Diego, California. She attended the San Diego State University, where she earned a scholarship in drama, and appeared on numerous theater productions.

Thompson is best known for her work on television as the Borg Queen on Star Trek: Voyager. For the same role, she attracted much controversy in an episode of Star Trek: Deep Space Nine entitled "Rejoined" for participating in one of television's first same-sex kisses.

Thompson was also noted for portraying the character Karen Sammler on Once and Again, from 1999 to 2002. During the early 1990s, she was offered various roles in both the big screen and the small scree. These included Silk Stalkings, A Woman Scorned: The Betty Broderick Story, Calendar Girl, Cop, Killer, and The Bambi Bembenek Story. She continued to acquire more guest roles on TV such as Dr. Greta Heints on Law and Order: SVU. She also made an appearance on Still Life and The Ballad of Jack and Rose.

In January 2006, Thompson found herself in a starring role on the short-lived NBC drama The Book of Daniel. She soon made appearances on two CBS series, NCIS as Army Lieutenant Colonel Hollis Mann and Without a Trace. Later, she took on roles in the drama American Pastime after her stint on an episode of CSI: Crime Scene Investigation. She also starred with Peter Fonda on the miniseries The Gathering.

In 2008, Thompson was given the role of Queen Rose Benjamin on the NBC drama Kings. As the first queen of Gilboa, Rose has to make sure that she accomplishes her duties, especially her son, Jack, succeeding his father’s throne.