Wilson was born in Detroit, Michigan, in 1951,but he grew up in Goleta, California, where he sometimes went by the stage name of "Goleta Slim." He started with the blues in the late 1960s and was tutored by people like Muddy Waters, Jimmy Rogers, Eddie Taylor, Albert Collins, George "Harmonica" Smith, Luther Tucker and Pee Wee Crayton and was influenced by harmonica players such as Little Walter, James Cotton, Big Walter Horton, Slim Harpo and Lazy Lester.
Before he moved to Austin, Texas, in 1974, he was the leader of the band Aces, Straights and Shuffles in Minneapolis, Minnesota; the band released one single. In Austin he formed the Fabulous Thunderbirds with guitarist Jimmie Vaughan.
They became the house band at Antone's, a blues club owned by Clifford Antone.
Wilson continues to perform up to 300 concert dates per year at blues music festivals and clubs all over the world, both as leader of the Fabulous Thunderbirds and with Kim Wilson's Blues Allstars.
His powerful style of blues harp playing has been described as "loaded with the textures of a full-blown horn section.
In 2015, Wilson made a guest appearance playing the harmonica on Karen Lovely's album, Ten Miles of Bad Road.
In 2016, Wilson won a Blues Music Award in the 'Instrumentalist - Harmonica' category.
Wilson plays himself in a rare television appearance on Wiseguy, "Sleepwalk" episode, 1989.