Miller won fame as a "blues shouter", a musician whose vocal force was powerful enough that it could be heard in an auditorium with a big band behind it even without using a microphone. He also occasionally performed on trombone. He recorded for Savoy Records early in his career, including with The Five Pennies as backing musicians. His jazz activities also included work with Count Basie and Duke Ellington. After performing with John Hendricks's revue, The Evolution of the Blues, Miller signed with Columbia Records and released several full-length albums. In the 1960s he had a short side career as an actor, appearing in small roles in The Big Meat Eater and It's a Mad Mad Mad Mad World.
In the 1970s Miller toured with Big Joe Turner, then moved to Canada, settling in Edmonton, Alberta. He lived there for the rest of his life, working with local musician Tommy Banks and covering "Big Yellow Taxi" with the song's author, Albertan Joni Mitchell. He was the subject of a documentary released by the National Film Board of Canada in 1987. Miller played a major role in the growth of the Edmonton Jazz Society, which began in the late 1970s, and taught at the Banff Centre for Fine Arts.
Jay McShann wrote a tribute piano solo piece to Miller, entitled "Big Miller's Blues".