Cotton became interested in music when he first heard Sonny Boy Williamson II on the radio. He left home to find Williamson in West Helena, Arkansas. For many years Cotton claimed that he told Williamson that he was an orphan, and that Williamson Boy took him in and raised him; a story he admitted in recent years is not true. Williamson did however mentor Cotton during his early years. When Williamson left the south to live with his estranged wife in Milwaukee, Wisconsin, he left his band in Cotton’s hands. Cotton was quoted as saying, “He just gave it to me. But I couldn’t hold it together ’cause I was too young and crazy in those days an’ everybody in the band was grown men, so much older than me.”
While he played a few instruments, Cotton was famous for his work on the harmonica.
Cotton began his professional career playing the blues harp in Howling Wolf‘s band in the early 1950s. He made his first recordings as a solo artist for the Sun Records label in Memphis,Tennessee in 1953. Cotton began to work with the Muddy Waters Band around 1955. He performed songs such as “Got My Mojo Working” and “She’s Nineteen Years Old“, although he did not appear on the original recordings; long-time Muddy Waters harmonica player Little Walter was utilized on most of Muddy’s recording sessions in the 1950s. Cotton’s first recording session with Waters took place in June 1957, and he would alternate with Little Walter on Muddy’s recording sessions until the end of the decade, and thereafter until he left to form his own band. In 1965 he formed the Jimmy Cotton Blues Quartet, utilizing Otis Spann on piano to record between gigs with Waters’ band. Their performances were captured by producer Samuel Charters on volume two of the Vanguard recording Chicago/The Blues/Today!. After leaving Muddy’s band in 1966, Cotton toured with Janis Joplin while pursuing a solo career. He formed the James Cotton Blues Band in 1967. They mainly performed their own arrangments of popular blues and R&B material from the 1950s and 1960s. Two albums were recorded live in Montreal that year.
In the 1960s, Cotton formed a big blues band in the tradition of Bobby “Blue” Bland. Four tracks that are extremely upbeat and feature the big band horn sound and five stripped down traditional songs recorded are captured on the album Two Sides of the Blue.
In the 1970s, Cotton recorded several albums with Buddah Records. Cotton played harmonica on Muddy Water’s Grammy Award winning 1977 album Hard Again, produced by Johnny Winter. The James Cotton Blues Band received a Grammy nomination in 1984 for Live From Chicago: Mr. Superharp Himself!, and a second for his 1987 release, Take Me Back. He finally was awarded a Grammy for Deep in the Blues in 1996 for Best Traditional Blues Album.
A throat problem left Cotton unable to sing from the mid 1990s onwards, but he continues to tour, utilizing singers or his backing band members as vocalists. Cotton’s latest album, Baby Don’t You Tear My Clothes, was released in 2004.
On March 10 2008, Cotton and Ben Harper inducted Little Walter into the Rock and Roll Hall of Fame. They performed “Juke” and “My Babe” together at the induction ceremony, which was broadcast nationwide on VH1 Classic. On july 19 2008, honorary award in Hondarribia blues festival, for all his career.