Masekela ''was born in Kwa-Guqa Township, Witbank, South Africa. He began singing and playing piano as a child. At age 14, after seeing the filmYoung Man With a Horn (in which Kirk Douglas plays a character modeled after American jazz trumpeter Bix Beiderbecke), he took up playing the trumpet. His first trumpet was given to him by Archbishop Trevor Huddleston, the anti-apartheid chaplain at St. Peter's Secondary School''.
Huddleston asked the leader of the then Johannesburg "Native" Municipal Brass Band, Uncle Sauda, to teach Masekela the rudiments of trumpet playing. Masekela quickly mastered the instrument. Soon, some of his schoolmates also became interested in playing instruments, leading to the formation of the Huddleston Jazz Band, South Africa's first youth orchestra. By 1956, after leading other ensembles, Masekela joined Alfred Herbert's African Jazz Revue''.