Ernie first was reared in Cincinnati, where his older brothers formed The Isley Brothers, first as a gospel group, then as a secular-singing group, until 1963 when he and his family moved to Englewood, New Jersey, where Ernie began to teach himself to become a musician. First skilled in drums, he moved on to guitar, bass and various other instruments.
After befriending future rock legend Jimi Hendrix, who was one of the touring guitarists for his brothers and actually lived at the Isleys home for a several years, and being influenced by Jose Feliciano's version of The Doors' Light My Fire, Ernie trained himself to be a guitarist.
In 1969, he, his baby brother Marvin and in-law relative Chris Jasper joined the Isleys' touring band. It was Ernie who played the memorable bass guitar riff on the Isleys' groundbreaking 1969 funk hit, "It's Your Thing". It wasn't until 1972's Brother, Brother, Brother, however, that Ernie and the younger Isley members began to play a role in the group's sound. After moving to Epic Records in 1973, Ernie, Marvin and Chris joined the Isleys as full-fledged members, a tenure they would share under the 3 + 3 moniker until 1983. Between those years, Ernie was notable for his guitar riffs in hits like "That Lady, Pt. 1 & 2", their version of Seals & Crofts' "Summer Breeze", their 1974 hit, "Live It Up", and their 1977 top 50 R&B ballad, "Voyage to Atlantis". Not only did he display his talent as a guitar player but also played drums on most of the Isleys' records after 1974.
Ernie was also an acclaimed songwriter penning, among others, the Isleys' funk anthems "Fight the Power Pts. 1 & 2" and "Take Me to the Next Phase" and softer ballads such as "Voyage to Atlantis", "At Your Best, You are Love" and "Between The Sheets". In 1984, Ernie, Marvin and Chris left the Isleys to form the splinter group, Isley-Jasper-Isley, a group that scored a couple of hits, including 1985's Caravan of Love and the Ernie-led ballad, Insatiable Woman before splitting up in 1987.
In 1990, he released his first and only solo album, High Wire. In the same year he recorded a cover version of the The Cars' "Let's Go" for the compilation Rubáiyát. The next year, he re-joined the Isleys with Ronald and Marvin. He has remained a member since then.
Ernie Isley currently resides in St. Louis, Missouri. He is involved in various music workshops held at local St. Louis middle and high schools. He also has a daughter, Alexandra, also a musician (singer) who will carry on the Isley's musical legacy. Ernie has finished his design and received his third "Zeal" guitar and is working on a solo album.