Ernie started playing drums at 12. His first live gig as a member of his brothers' band was as a drummer in 1966 at the age of 14. Ernie was influenced by José Feliciano's version of "Light My Fire" and in 1968 got his first guitar. He is a self-taught musician. In 1968 he did his first professional recording, playing bass on the Isleys' breakthrough funk smash "It's Your Thing", released in 1969. He played electric guitar, acoustic guitar, and drums on the group's early 1970s' albums Get Into Something, Givin' It Back, and Brother, Brother, Brother, before fully joining The Isley Brothers in 1973, becoming a multi-instrumentalist playing acoustic guitar, electric guitar, drums and percussion.
In 1990, Ernie released his first solo album, 'High Wire'.
The Isley Brothers were inducted into the Rock n' Roll Hall of Fame in 1992.
In 2014 the Isley Brothers received the Grammy Lifetime Achievement Award.