Born in Scott, Mississippi, to a sharecropping family, Broonzy learned the rudiments of the fiddle before his family moved to Arkansas. By the age of fourteen, he was working for tips at country dances and picnics. In the early 1920s, he moved to Chicago, where, under the guidance of Papa Charlie Jackson, he learned to play blues guitar. Big Bill Broonzy's brand of blues stretched from ragtime-influenced blues, to city blues backed with jazz musicians, to traditional folk blues and spirituals. He is considered the godfather of the Chicago blues scene.

Broonzy influenced many young bluesmen, and he often took artists of lesser stature under his wing, helping them secure recording sessions and performance dates. His stature as a blues artist grew far beyond the Chicago scene after his performances at John Hammond's famous Spirituals to Swing concert series in 1938 and 1939 at Carnegie Hall in New York City.

In 1951, Broonzy toured Europe, helping to introduce blues to France and England and opening the door for other American blues artists. In 1955, with help from writer Yannick Bruynoghe, he wrote his autobiography, Big Bill's Blues. Originally published in London, the book was one of the earliest autobiographies by a bluesman. Two years later, Broonzy was diagnosed with throat cancer. He continued to perform, often in great pain, until he died of the disease in 1958. Broonzy was inducted into Blues Foundation's Hall of Fame in 1980.