Bessie Smith was born in Chattanooga, Tennessee, on April 15, 1892, though the record is untidy: the 1900 census has her family reporting July 1892, while the 1910 census gives a birth date of April 15, 1894, the day her family observed as her birthday. Her father, William, was a laborer and part-time Baptist preacher who died before she could remember him. By the time she was nine her mother and a brother had also died, and her older sister Viola took charge of the children. Bessie and her brother Andrew busked on the streets of Chattanooga, she singing and dancing while he played guitar, usually in front of the White Elephant Saloon at Thirteenth and Elm. In 1912 her brother Clarence, who had left in 1904 with a traveling troupe, brought her to audition for the managers of the Moses Stokes company, Lonnie and Cora Fisher. She was hired as a dancer, because the troupe already had a star singer in Ma Rainey, who is thought to have helped her develop stage presence without teaching her to sing. By about 1913 she was building her own act at the "81" Theater in Atlanta, and she rose to become the top attraction on the Theatre Owners Booking Association circuit, the Black vaudeville and tent-show network of the South and East Coast.

The recording business came to her after Mamie Smith's "Crazy Blues" (Okeh, 1920) sold more than 100,000 copies and showed record companies a Black audience. Frank Walker signed Bessie Smith to Columbia in 1923, and her first session took place on February 15, 1923. Her first record paired "Down Hearted Blues," with Clarence Williams at the piano, and "Gulf Coast Blues." Both sides were hits, and "Down Hearted Blues" is credited with 780,000 copies sold in its first six months. On September 26, 1923 she cut "Cemetery Blues," the first record issued when Columbia opened its "race records" series. She married Jack Gee on June 7, 1923, and over the next several years she became the highest-paid Black entertainer of her day, heading shows of as many as forty performers and traveling in her own 72-foot railroad car. Columbia's publicity department called her the Queen of the Blues; the national press upgraded the title to Empress of the Blues. Her electrical recording debut came on May 5, 1925 with "Cake Walking Babies (From Home)."

Her jazz connection is documented in the musicians who stood behind her. Fletcher Henderson was her pianist on dozens of sides between 1923 and 1927. On January 14, 1925, in Columbia's New York studio, she recorded five numbers with Louis Armstrong on cornet and Fred Longshaw on organ: "St. Louis Blues," "Reckless Blues," "Sobbin' Hearted Blues," "Cold in Hand Blues" and "You've Been a Good Ole Wagon." The "St. Louis Blues" is the recording most often cited from the meeting, and it was inducted into the Grammy Hall of Fame in 1993 in the jazz category. Over the following years her Columbia sessions drew in Joe Smith, Tommy Ladnier and Demas Dean on cornet, Charlie Green and Jimmy Harrison on trombone, Don Redman and Buster Bailey on clarinet. At a band session on March 2, 1927 she recorded "After You've Gone," "Alexander's Ragtime Band," "Muddy Water (A Mississippi Moan)" and "There'll Be a Hot Time in the Old Town Tonight" with Fletcher Henderson, Joe Smith, Jimmy Harrison, Charlie Dixon, Buster Bailey and Coleman Hawkins on clarinet. On February 17, 1927 she recorded "Back-Water Blues" and "Preachin' the Blues" with only James P. Johnson at the piano, and Johnson returned for a run of sessions through 1929. "Empty Bed Blues," cut on March 20, 1928 with Porter Grainger on piano and Charlie Green on trombone, became the most notorious record of her career and entered the Grammy Hall of Fame in 1983. In all she recorded 156 tracks for Columbia and four for Okeh between 1923 and 1933.

The Depression and the arrival of sound film cut into her work, and she never stopped performing. In 1929 she appeared in the Broadway musical Pansy, which failed, though critics singled her out as its one asset. That year she also made her only film, the two-reel St. Louis Blues, directed by Dudley Murphy and shot in Astoria, Queens, with W. C. Handy as co-author and musical director. She sings the title song in a speakeasy scene backed by James P. Johnson at the piano, the cornetists Thomas Morris and Joe Smith, Bernard Addison on guitar and banjo, and the Hall Johnson Choir. The film was selected for the National Film Registry in 2006.

Her last recordings came on November 24, 1933, when John Hammond arranged four sides for Okeh, paying a flat $37.50 for each. The band was the swing-era New York pool: trombonist Jack Teagarden, trumpeter Frankie Newton, tenor saxophonist Chu Berry, pianist Buck Washington, guitarist Bobby Johnson and bassist Billy Taylor. Benny Goodman, recording with Ethel Waters in the neighboring studio, dropped in and can barely be heard on one selection. The session produced "Take Me for a Buggy Ride" and "Gimme a Pigfoot," both by Wesley Wilson, and a version of her blues that fit the swing era; Hammond, who had wanted the older sound, was not entirely pleased.

On September 26, 1937, she was badly hurt in a car crash on U.S. Route 61 between Memphis and Clarksdale, Mississippi. Her partner Richard Morgan, an uncle of Lionel Hampton, was driving and hit the back of a slow-moving truck. Dr. Hugh Smith, a Memphis surgeon who reached the scene first, found her right arm nearly severed at the elbow and later attributed her death to crushing injuries along that whole side of her body. She was taken to the G. T. Thomas Afro-American Hospital in Clarksdale, where the arm was amputated, and she passed away that morning without regaining consciousness. She was 45. The story that a whites-only hospital turned her away, which John Hammond put into print in DownBeat that November and which Edward Albee used in his 1959 play The Death of Bessie Smith, has been discredited: Dr. Smith told her biographer Chris Albertson that an ambulance carrying a Black patient would not have gone to a white hospital in that part of Mississippi. Her funeral in Philadelphia on October 4, 1937 drew thousands, and her grave stayed unmarked until August 7, 1970, when a headstone paid for by the singer Janis Joplin and by Juanita Green, who had done housework for her as a child, was erected.

Recognition followed, much of it posthumous: the Blues Hall of Fame (1980), the Big Band and Jazz Hall of Fame (1981), the National Women's Hall of Fame (1984), a Grammy Lifetime Achievement Award and an "early influences" induction into the Rock and Roll Hall of Fame (both 1989), a U.S. postage stamp (1994), the Library of Congress National Recording Registry for "Down Hearted Blues" (2002), and the Nesuhi Ertegun Jazz Hall of Fame at Jazz at Lincoln Center (2008). Rolling Stone ranked her No. 33 on its 2023 list of the 200 greatest singers. In 2015 HBO's Bessie, with Queen Latifah in the title role, won four Primetime Emmy Awards.

Smith's genre is classic blues, sung in the vaudeville and tent-show tradition, and the jazz label fits her through company and repertoire more than through improvisation: the cornetists, trombonists and pianists who accompanied her were the leading jazz players of the 1920s, and her songbook ran through "St. Louis Blues," "After You've Gone" and "Alexander's Ragtime Band." The nearest canonical tags are Jazz Blues and Vocal Jazz. She sang as a powerful contralto whose force was obvious from her first session, made in the acoustic era, and became more striking once electrical recording arrived in 1925. Danny Barker and Tommy Dorsey both compared her hold on an audience to that of a preacher. Her lyrics spoke about poverty, prison and the chain gang ("Jail House Blues," "Sing Sing Prison Blues," "Poor Man's Blues," "Washwoman's Blues"), jealousy and drink, and a woman's right to desire and independence, subjects that critics outside her audience found coarse and that scholars now read as an early strand of African American protest song.

Her influence runs through the jazz singers who followed. Billie Holiday named her among the records that first mattered to her, and Dinah Washington recorded the tribute album Dinah Sings Bessie Smith in 1958, the same year LaVern Baker released a tribute of her own. Technical faults in the original masters, including speed variations and off-center spindle holes, distorted pitch and phrasing on many reissues, and the transfers John R. T. Davies made for Frog Records are widely preferred to the first Columbia compact discs.