Blondell was born to a vaudeville family in New York City. Her father, known as Eddie Joan Blondell, Jr., was born in Indiana in 1866 to French parents, and was a vaudeville comedian and one of the original Katzenjammer Kids. Blondell's mother was Kathryn ("Katie") Cain, born April 13, 1884, in Brooklyn of Irish American parents. Her younger sister, Gloria, also an actress, was briefly married to film producer Albert R. "Cubby" Broccoli (the future producer of the James Bond film series) and bears a strong resemblance to her older sister, Joan. Blondell also had a brother, the namesake of her father and grandfather. Her cradle was a property trunk as her parents moved from place to place and she made her first appearance on stage at the age of four months when she was carried on in a cradle as the daughter of Peggy Astaire in The Greatest Love.
Joan had spent six years in Australia and seen much of the world by the time her family, who had been on tour, settled in Dallas, Texas when she was a teenager. Under the name Rosebud Blondell, she won the 1926 Miss Dallas pageant and placed fourth for Miss America in Atlantic City, New Jersey, in September of that same year. She attended what is now the University of North Texas, then a teacher's college, in Denton, where her mother was a local stage actress, and she worked as a fashion model, a circus hand, and a clerk in a New York store. Around 1927, she returned to New York, joined a stock company to become an actress, and performed on Broadway. In 1930, she starred with James Cagney in Penny Arcade.
Penny Arcade only lasted three weeks, but Al Jolson saw it and bought the rights to the play for $20,000. He then sold the rights to Warner Brothers with the proviso that Blondell and Cagney be cast in the film version. Placed under contract by Warners, she moved to Hollywood where studio boss Jack Warner wanted her to change her name to "Inez Holmes", but Blondell refused. She began to appear in short subjects, and in 1931 was named as one of the WAMPAS Baby Stars.
During the 1930s Joan Blondell would embody the Depression era gold-digger, and with her huge blue eyes, blonde hair and wise cracking personality, became a crowd favorite. She appeared in more Warners films than any other actress, and referred to herself as "Warner's workhorse." The popularity of her films made a great contribution to the studio's profitability.
Blondell was paired with James Cagney in such films as Sinners' Holiday (1930) – the film version of Penny Arcade – and The Public Enemy (1931), and was one half of a gold-digging duo with Glenda Farrell in nine films. During the Great Depression, Blondell was one of the highest paid individuals in the United States. Her stirring rendition of "Remember My Forgotten Man" in the Busby Berkeley production of Gold Diggers of 1933, in which she co-starred with Dick Powell and Ginger Rogers, became an anthem for the frustrations of the unemployed and the government's failed economic policies. (Even though she was cast in many of the classic Warners musicals, she was not a singer, and in the Forgotten Man number, she mostly talked and acted her way through the song.) In 1937, she starred opposite Errol Flynn in The Perfect Specimen, from a screenplay by the then "hot" playwright Lawrence Riley and others.
By the end of the decade, she had made nearly fifty films, despite having left Warner Bros. in 1939. Continuing to work regularly for the rest of her life, Blondell was well received in her later films, despite being relegated to character and supporting roles after the mid-1940s (she was billed below the title for the first time in 14 years in 1945's Adventure, which starred Clark Gable and Greer Garson), and received an Academy Award for Best Supporting Actress nomination for her role in The Blue Veil (1951). She was also featured prominently in A Tree Grows in Brooklyn (1945); Nightmare Alley (1947); The Opposite Sex (1956) (which paired her with ex-husband Dick Powell's wife, June Allyson); Desk Set (1957) and Will Success Spoil Rock Hunter? (1957). She received considerable acclaim for her performance as Lady Fingers in Norman Jewison's The Cincinnati Kid (1965), garnering Golden Globe nomination and National Board of Review win for Best Supporting Actress. Blondell was widely seen in two films released not long before her death, Grease (1978) and the remake of The Champ (1979) with Jon Voight and Rick Schroder. In addition, John Cassavetes cast her as a cynical, aging playwright in his film Opening Night (1977).
Blondell also appeared in various television programs, including the episode "You're All Right, Ivy" of Jack Palance's circus drama, The Greatest Show on Earth, which aired on ABC in the 1963—1964 television season. Her co-stars in the segment were Joe E. Brown and Buster Keaton. In 1965, she was in the running to replace Vivian Vance as Lucille Ball's sidekick on the hit CBS television comedy series, The Lucy Show. Unfortunately, after filming her second guest appearance as 'Joan Brenner' (Lucy's new friend from California), Blondell walked off the set right after the episode had completed filming when Ball humiliated her by harshly criticizing her performance in front of the studio audience and technicians.
Blondell continued working on television. In 1968, she guest-starred on the CBS-TV sitcom Family Affair. She also replaced Bea Benaderet, who was ill, for one episode on the CBS television series Petticoat Junction. In that installment, Blondell played FloraBelle Campbell, a lady visitor to Hooterville, who had once dated Uncle Joe (Edgar Buchanan) and Sam Drucker (Frank Cady). That same year, Blondell co-starred in the ABC western series Here Come the Brides set in the Pacific Northwest of the 19th century. Her co-stars included singer Bobby Sherman and actor-singer David Soul (who would later go on to star in ABC's Starsky and Hutch). Here Come The Brides was very popular in its first season, garnering nice ratings in its 7:30 P.M. time slot on Wednesday nights. However, for its second year, ABC moved it to a later time slot on Friday evenings. The ratings declined and the show was canceled in the spring of 1970. For her performance as Lottie Hatfield in this series, Blondell received two consecutive Emmy nominations for outstanding continued performance by an actress in a dramatic series.
In 1972 she had an ongoing supporting role in the NBC series Banyon, as Peggy Revere who operated a secretarial school in the same building as the Banyon detective agency. This was a 1930's period drama. Her students worked in Banyon's office, providing fresh faces for the show weekly. The show failed and was replaced mid-season.
Blondell has a star on the Hollywood Walk of Fame for her contribution to Motion Pictures, at 6309 Hollywood Boulevard. In December 2007, the Museum of Modern Art in New York City mounted a retrospective of Blondell's films in connection with a new biography by film professor Matthew Kennedy.
Blondell was married three times, first to cinematographer George Barnes in a private wedding ceremony on 4 January 1933 at the First Presbyterian Church in Phoenix, Arizona. They had one child — Norman S. Powell, who became an accomplished producer, director, and television executive — and divorced in 1936. On 19 September 1936, she married her second husband, actor, director, and singer Dick Powell. They had a daughter, Ellen Powell, who became a studio hair stylist, and Powell adopted her son by her previous marriage. Blondell and Powell were divorced on 14 July 1944.
On 5 July 1947, Blondell married her third husband, producer Mike Todd, whom she divorced in 1950. Her marriage to Todd was an emotional and a financial disaster. She once accused him of holding her outside a hotel window by her ankles. He was also a heavy spender who lost hundreds of thousands of dollars gambling (high-stakes bridge was one of his weaknesses) and went through a controversial bankruptcy during their marriage. An often-repeated myth is that Mike Todd "dumped" Joan Blondell for Elizabeth Taylor. In actuality, Blondell left Todd of her own accord years before he met Taylor.
She died of leukemia in Santa Monica, California, on Christmas Day 1979 at the age of 73 with her children and her sister at her bedside. She is interred in the Forest Lawn Memorial Park Cemetery in Glendale, California.
She wrote a novel titled Center Door Fancy (New York: Delacorte Press, 1972), which was a thinly disguised autobiography.