Freeman was one of the young musicians inspired by New Orleans ensembles and the innovations of Louis Armstrong to synthesize the Chicago style in the late 1920s. By the 1930s he was working in New York City, typically in the company of ex-Chicagoans, especially Eddie Condon, in whose band Freeman recorded a noted solo, “The Eel” (1933). By then he had developed a fluent, romantic style featuring sinuous legato melodies. His tenor saxophone sound was especially distinctive—full and smooth, with a rough edge and a large vibrato—and he played with a robust, at times almost violent swing. Along with a Chicago friend, drummer Dave Tough, Freeman played in the big bands of Tommy Dorsey (1936–38) and Benny Goodman (1938) before embarking on a freelance career as bandleader and soloist.

Freeman led a U.S. Army dance band based in the Aleutian Islands during World War II, then lived in New York and Chile. He often reunited with Condon and other former Chicagoans in concert. Among his notable albums are The Bud Freeman All-Stars and the 1957 Cootie Williams–Rex Stewart album, The Big Challenge, which brought together Freeman and his great tenor saxophone rival, Coleman Hawkins. After touring with the World's Greatest Jazz Band (1969–71), Freeman lived in England (1974–80) and performed there and in Europe; thereafter he was based again in Chicago. He wrote two short volumes of reminiscences, You Don't Look Like a Musician (1974) and If You Know of a Better Life, Please Tell Me (1976), and an autobiography, Crazeology (with Robert Wolf, 1989).