Barbeau was born in Sacramento, California, the daughter of Armen (née Nalbandian) and Joseph Barbeau, who was a public relations executive for Mobil Oil. Barbeau's father was French-Canadian and her mother Armenian-American. She attended Del Mar High School in San Jose, California. In her autobiography, Barbeau says that she first caught the show business bug while entertaining troops at army bases throughout Southeast Asia, touring with the San Jose Civic Light Opera. She has a sister Jocelyn and a half brother on her father's side, Robert Barbeau, who still resides in the Sacramento area.

In the late 1960s Barbeau moved to New York City and worked "for the mob" as a go-go dancer, as well as appeared Off-Broadway in a "nudie musical" called Stag Movie before making her Broadway debut in Fiddler on the Roof, playing Tevye's daughter, Hodel, alongside Bette Midler. Adrienne has since starred in over 25 musicals and plays, among them, Women Behind Bars, The Best Little Whorehouse in Texas and Grease, as tough-girl "Rizzo", for which she received a Theater Guild Award and a 1972 Tony Award nomination.

During the 1970s Barbeau starred as the daughter of Bea Arthur's title character in the comedy series Maude which ran from 1972 to 1978. In her autobiography There Are Worse Things I Could Do she remarked: "What I didn't know is that when I said [my lines] I was usually walking down a flight of stairs and no one was even listening to me. They were just watching my breasts precede me." During the last 2 seasons of Maude, she did not appear in the majority of the episodes, after her name became a celebrity status. In a 2009 Entertainment Tonight TV interview, Barbeau mentioned that she had an on- and off-camera chemistry with Arthur. She also told Entertainment Tonight, the two stayed close until Arthur's death on April 25, 2009. Barbeau and Arthur reunited on camera during a 2007 taping of The View, reminiscing about their long-running friendship and their years as costars on Maude.

Barbeau, who played the role of Mrs. Findlay's TV daughter, said about the popularity her character scored on Maude, alongside Arthur, about her portrayal: "Thousands of people came up to me and said, 'I got an aunt who's just like Maude, my mother is just like Maude. I think many, many people related to Bea's character, in that way. There were others who found her too abrasive who didn't like the character, and that big woman with a low voice, saying those things." Barbeau also said of the way that Beatrice wanted to entertain the audience on Maude, "I at least was; and I'm sure that Bea was very proud of being something that was socially significant that was entertaining people, and making them laugh, at the same time, slipping her philosophy." Barbeau said of her mentor's decision in leaving the show was, "I think she was tired, but I also knew she wanted to go out strong, yet, we were still in the Top 20, right through the sixth season, but I think she was probably feeling, 'How many more scripts are there'?, and you know, where we can be as good as we've been!" The last thing Adrienne said prior to the cancelation of Maude was: "It was wonderful, all the way through, and so much of that was because of Bea, because, we had such a great group of people that were were working with, who, were were like a family." For 35+ years, Barbeau continued to be a good friend to Arthur until her death in 2009, long after the cancelation of Maude. In addition, Rebecca's (Beatrice’s real-life mother) death in 1986, drew Arthur & Barbeau real closer, as Barbeau delivered her condolences to her on-screen mother; while enjoying her success as a movie actress, 23 yrs. before Arthur’s own death. Her series’ star said on The View, Arthur had occasionally visit her twins.[citation needed]

Barbeau was cast in numerous television films and shows such as The Love Boat, Fantasy Island, Valentine Magic on Love Island, and Battle of the Network Stars. In her autobiography she claimed: "I actually thought CBS asked me to be on Battle of the Network Stars because they thought I was athletic. My husband clued me in: who cared if I won the race, as long as I bounced when I ran?"

The popularity of Barbeau's 1978 cheesecake poster confirmed her status as a sex symbol. Barbeau's popularity stemmed partly from what critic Joe Bob Briggs referred to as the "two enormous talents on that woman," and her typecasting as a "tough broad". Despite her initial success, she said at the time that she thought of Hollywood as a "flesh market", and that she would rather appear in films that "explore the human condition" and "deal with issues".

Barbeau was cast by her then-husband, director John Carpenter, in his 1980 horror film, The Fog, which was her first theatrical film appearance. The film was released in on February 1, 1980 and was a theatrical success, grossing over $21 million in the United States alone, and establishing Barbeau as a genre film star. She subsequently appeared in a number of early-1980s horror and science fiction films, a number of which have now become cult film classics, including Escape from New York (also from Carpenter), Creepshow and Swamp Thing.

She also appeared in the high grossing Burt Reynolds comedy The Cannonball Run in 1981 and as the shrewish wife of Rodney Dangerfield in Back to School (1986). Barbeau also starred along with talk show host Bill Maher and Shannon Tweed in Cannibal Women in the Avocado Jungle of Death.

In the 1990s, Barbeau mostly appeared in made-for-television films such as Scott Turow's The Burden of Proof in 1992, as well as playing Oswald's mother on The Drew Carey Show and gaining new-found fame among animation fans as Catwoman on Batman: The Animated Series and Gotham Girls. Coincidentally, Barbeau's on-screen son on The Drew Carey Show, Diedrich Bader would go on to perform the voice of Batman on the animated series Batman: The Brave and the Bold.

She also worked as a television talk show host and a weekly book reviewer for KABC talk radio in Los Angeles. In 1999, she guest starred in the Star Trek: Deep Space Nine episode "Inter Arma Enim Silent Leges" as Romulan Senator Kimara Cretak.