Tammy Bruce collaborated with Los Angeles professional women to create one of the first ad-hoc independent pro-choice activist groups. The group's early feminist activism began in 1987. This group confronted anti-abortion group protesters, and helped develop a strategy to stop "Operation Rescue" from successfully blocking the entrance to abortion clinics. During the years 1987-1990 she also participated in the Los Angeles chapter of the AIDS activist group AIDS Coalition to Unleash Power (ACT-UP).

For seven years, Bruce served as president of the Los Angeles chapter of the National Organization for Women (NOW) (1990—1996). Bruce served two years on NOW's board of directors, but later criticized the organization in a book. During the early 1990s, she spearheaded the campaign to alert the public to the sexualized violence in the novel American Psycho, and led an effort to boycott all titles by that publisher, Knopf, for a year.

In 1996, the NOW Executive Board voted nearly unanimously to censure Bruce for what it claimed were "racially insensitive comments" during the O.J. Simpson murder trial. After months of infighting, Bruce resigned as president of Los Angeles NOW in June 1996. Bruce claimed that the censure was due to her focus on domestic violence, as opposed to defense attorney Johnnie Cochran's "racial issues" trial argument. Since then, Bruce has written about the dispute in her critique on what she sees as the failings of NOW, and the political left in general. She believes that the feminist establishment in the U.S. has abandoned authentic feminism.

In 2004, Bruce argued that gay Americans were not uniformly supportive of same-sex marriage and stated that she respected the opinion that marriage should be restricted to heterosexual couples. She described civil unions as an alternative providing equal rights.

In her book The Death of Right and Wrong, Tammy Bruce writes of her involvement with Brenda Benet, who killed herself in a home she had shared with Bruce. They were romantically involved for a time after Benet left Bill Bixby. Bruce had moved out two weeks prior to Benet's suicide. On the day of the suicide, Bruce thought that she would meet Benet for lunch. According to Bruce, Benet was locked inside the bathroom of her home when she arrived. She sensed something was wrong and went to get help. After Bruce stepped outside, Benet shot herself. The book Soap Opera Babylon said that Benet was involved with a male costar on Days of our Lives until just before she killed herself.

Bruce holds a bachelor's degree in Political Science from the University of Southern California. In the past, Bruce described herself as a "lifelong Democrat", but FEC records show she has since 2005 contributed primarily to Republicans, and she has stated on both her radio program and blog that she is now registered as a "Decline-to-State" as of February 2008. She considers herself an independent conservative.

Tammy Bruce made her film debut in 2081, an independent film based on Kurt Vonnegut's short story "Harrison Bergeron". Bruce plays the role of Diana Moon Glampers, the United States Handicapper General in a technologically advanced, totalitarian, fascist state. Bruce's character commits murder on live television. The film was released in January 2010.