Rivers was born Joan Alexandra Molinsky in Brooklyn, New York, the daughter of Russian Jewish immigrants Beatrice (née Grushman) and Meyer C. Molinsky, who was a doctor. She was raised in Brooklyn, New York and her family later moved to Larchmont in Westchester County, NY. She attended Connecticut College between 1950 and 1952, and graduated from Barnard College in 1954 with a B.A. in English and anthropology. Before entering show business, Rivers worked as a fashion consultant at Bond Clothing Stores.

In the 1960s, Rivers made television appearances as a comedian on the popular shows The Tonight Show and The Ed Sullivan Show, as well as hosting the first of her several talk shows. Later in that decade she made a brief but notable appearance opposite Burt Lancaster in the film, The Swimmer. She was also a regular gag writer and performer on TV's Candid Camera.

In the 1970s, Joan Rivers appeared often as a guest on various television comedy and variety shows. One notable appearance on The Carol Burnett Show had her spoofing Valerie Harper in Rhoda (Rivers' character was named "Rhonda"), to the delight of the audience. From 1972 to 1976, she was the narrator for The Adventures of Letterman, an animated segment for The Electric Company.

In 1978, Rivers directed and wrote the film Rabbit Test starring her friend Billy Crystal, an avant garde movie about a man who gets pregnant, but it had disappointing results at the box office.

Rivers was the opening act for singer Helen Reddy on the Las Vegas Strip during the 1970s. She would eventually become a headliner in her own right to standing-room crowds continuing into the 1980s. Rivers also recorded a popular record album of her live stand-up act entitled What Becomes a (Semi) Legend Most?

Rivers continued to gain acclaim on television as she was often guest host of The Tonight Show throughout the early 1980s.

In 1986, Rivers hosted her own evening talk show, The Late Show Starring Joan Rivers, on the then-fledgling Fox Television Network; her talk show was one of the launch shows for the new network. The show lasted about a year. In 1983, Rivers had become the permanent guest host for Johnny Carson on The Tonight Show.

Carson was so upset by her decision to leave The Tonight Show without discussing it with him that he banned her from his show, even after Rivers' show failed. Rivers reportedly tried to call Carson on the phone personally after the Fox deal was announced; when he answered, she talked to him, but Carson hung up on her. The two never did reconcile before Carson died in 2005.

Soon after the cancellation of her series, Rivers saw a published interview claiming that her husband Edgar Rosenberg, who was a producer on her show, had tried to drive her insane during his illness. According to the interview, she was reported to have commented, "...I think things are just about finished with Edgar" and referred to her former boss at the Fox Network as "Barry (expletive) Diller." Rivers then went public with the news, saying in tears that a "Ben Hacker" had fabricated the story with what she called "vicious lies." A suit was filed against "Hacker."

In 1988, Rivers guest-starred on the Pee-Wee's Playhouse Christmas Special, along with other stars, which included Oprah Winfrey, Charo, and Cher. In some sense, it was Rivers' way of repaying Paul Reubens (creator of the character Pee-Wee Herman, and the show) who was the very first guest on her talk show when it premiered in 1986.

Not long after this, Rosenberg committed suicide, devastating Rivers. In her book, Bouncing Back, she describes how she developed bulimia and contemplated suicide. Eventually she recovered with counseling and the support of her family.

Eventually she returned to television with her own daytime talk show, The Joan Rivers Show, which ran from 1989 until 1994. Her enormous stock of bored husband jokes could no longer be used. A Rivers favorite had been: "When Edgar and I were first married, we'd play 'catch me, catch me!' and we'd run around the house. We still play 'catch me, catch me!' but now we walk."

Beginning in 1997, Rivers hosted her own radio show on WOR in New York. In 2003, Rivers and the station mutually decided to part ways.