Lightnin' Slim was born Otis V. Hicks on a farm outside St. Louis, Missouri. moving to Baton Rouge, Louisiana at the age of thirteen. Taught guitar by his older brother Layfield, Slim was playing in bars in Baton Rouge by the late 1940s.
He debuted on J. D. "Jay" Miller's Feature Records label in 1954 with "Bad Luck Blues". Slim then recorded for Excello Records for twelve years, starting in the mid-1950s, often collaborating with his brother-in-law, Slim Harpo and with harmonica player Lazy Lester.
In the 1970s, Slim performed on tours in Europe, both in the United Kingdom and at the Montreux Jazz Festival in Switzerland where he was often accompanied by Moses "Whispering" Smith on harmonica. He last toured the UK in 1973, with the American Blues Legends package.
In July 1974, Slim died of stomach cancer in Detroit, Michigan, aged 61.