Born in Los Angeles, California, she was the daughter of actor Robert Montgomery and his wife, Elizabeth Bryan Allen.

She is best remembered for her leading role as the witch Samantha in the ABC situation comedy Bewitched. This show was a huge success during its eight-year run from 1964 to 1972 and remains popular through syndication and the 2005 movie remake starring Will Ferrell and Nicole Kidman. Montgomery received five Emmy Award and four Golden Globe nominations for her role as Samantha.

Montgomery made her television debut in her father's series Robert Montgomery Presents, and her film debut in 1955 in The Court Martial of Billy Mitchell. Her early career then languished, consisting of supporting roles and appearances in television series.

Montgomery refused to do Samantha's famous nose twitch for fans after Bewitched went off the air, and was reluctant to discuss this role. She spent the remainder of her career pursuing dramatic roles that took her as far away from the good-natured Samantha typecasting as possible. She received Emmy Award nominations for playing a rape victim in A Case of Rape (1974), for her portrayal of the notorious Lizzie Borden in The Legend of Lizzie Borden (1975), and for her role as a strong woman facing hardship in 1820's Ohio in the mini-series The Awakening Land (1978). She also made a chilling villain in the 1985 picture Amos, playing a nurse in a state home who terrorized residents Kirk Douglas and Dorothy McGuire. Her final acting role was in an episode of Batman: The Animated Series entitled "Showdown," in which she played a barmaid.

She was married to actor Gig Young from 1956 to 1963; to Bewitched producer William Asher from 1963 to 1973, with whom she had 3 children; had an affair with Richard Michaels the director of Bewitched, for a year before they finally came out with the truth. Her marriage to William Asher ended and so did Bewitched (through Bill's own admission that he was involved with a woman named Nancy Fox who was an extra on the set). She moved out of her house, moved in with Michaels, and they lived together for two years before they broke up because of guilt. She was married to actor Robert Foxworth, (with whom she had been living for over 20 years) from 1993 until her death.

She had an older sister, Martha Bryan Montgomery, who died before Elizabeth was born, and a brother, Robert Montgomery Jr., who was born in 1936.

Elizabeth Montgomery died of colorectal cancer on May 18, 1995, at the age of 62. She died just eight weeks after being diagnosed with the disease. At the time of her death, the media widely reported that she had ignored the symptoms of her illness until it was too late, as she was caring for Robert Foxworth, who had had hip replacement surgery.

Unwilling to die in a hospital, and with no hope of recovery, she elected to return to her Beverly Hills home that she shared with Foxworth; she died there with Robert and her children waiting outside of the bedroom at her request.

Her remains were cremated shortly after her death.