Born in Jackson, Mississippi, United States, Spann became known for his distinct piano style.Spann's father was reportedly a pianist called Friday Ford. His mother Josephine Erby was a guitarist who had worked with Memphis Minnie and Bessie Smith, and his stepfather Frank Houston Spann was a preacher and musician. One of five children, Spann began playing piano at the age of seven, with some instruction from Friday Ford, Frank Spann, and Little Brother Montgomery. By age 14, he was playing in bands in the Jackson area. Big Maceo Merriweather mentored the young musician after his arrival in Chicago in 1946. Spann performed as a solo act or teamed up with guitarist Morris Pejoe, working a regular spot at the Tic Toc Lounge.Spann replaced Merriweather as Muddy Waters' piano player in late 1952, and participated in his first recording session with the band on September 24, 1953. He continued to record as a solo artist and session man with other musicians, including Bo Diddley and Howlin' Wolf during his tenure with the group. He stayed with Muddy Waters until 1968.Spann's work for Chess Records included the 1954 single, "It Must Have Been the Devil" / "Five Spot", with B.B. King and Jody Williams on guitars. In 1956 he recorded two unreleased tracks with Big Walter Horton and Robert Lockwood. He recorded a session with the guitarist Robert Lockwood, Jr. and vocalist St. Louis Jimmy in New York on August 23, 1960, which was issued on Otis Spann Is The Blues
and Walking The Blues
. A 1963 effort with Storyville Records was recorded in Copenhagen. He worked with Muddy Waters and Eric Clapton on Decca Records and with James Cotton for Prestige in 1964.The Blues is Where It's At
, Spann's 1966 album for ABC-Bluesway, includes artists George "Harmonica" Smith, Muddy Waters, and Sammy Lawhorn. The Bottom of the Blues
(1967), featuring Spann's wife, Lucille Jenkins Spann (June 23, 1938 – August 2, 1994), was released on Bluesway. He worked on albums with Buddy Guy, Big Mama Thornton, Peter Green, and Fleetwood Mac during the 1960s.Material featuring Spann on DVD includes the Newport Jazz Festival (1960), the American Folk Blues Festival (1963), The Blues Masters (1966), and the Copenhagen Jazz Festival (1968).
Spann died of liver cancer in Chicago in 1970. He was buried in the Burr Oak Cemetery, Alsip, Illinois. Spann's grave laid unmarked for almost thirty years, until Steve Salter (president of the Killer Blues Headstone Project) wrote a letter to Blues Revue magazine to say "This piano great is lying in an unmarked grave. Let's do something about this deplorable situation". Blues enthusiasts from around the world sent donations to purchase Spann a headstone. On June 6, 1999 the marker was unveiled during a private ceremony. The stone reads "Otis played the deepest blues we ever heard - He'll play forever in our hearts".He was posthumously elected to the Blues Hall of Fame in 1980.