Blackwell was born in Syracuse, North Carolina, United States as one of sixteen children of Payton and Elizabeth Blackwell. Part Cherokee, he grew up and spent most of his life in Indianapolis, Indiana. Blackwell was given the nickname, \"Scrapper\", by his grandmother, due to his fiery nature.[3] His father played the fiddle, but Blackwell was a self-taught guitarist, building his first guitar out of cigar boxes, wood and wire. He also learned the piano, occasionally playing professionally. By his teens, Blackwell was a part-time musician, traveling as far as Chicago. Known for being withdrawn and hard to work with, Blackwell established a rapport with pianist Leroy Carr, whom he met in Indianapolis in the mid-1920s, creating a productive working relationship. Carr convinced Blackwell to record with him for the Vocalion label in 1928;[4] the result was \"How Long, How Long Blues\", the biggest blues hit of that year.