Campbell was born in Duncan, Mississippi. He moved to Chicago at the age of ten, and by age 12 was learning from the blues musicians Muddy Waters, Magic Sam, and Otis Rush.

In his early years as a professional musician, he played as a sideman with Howlin’ Wolf, Little Walter, Little Johnny Taylor, and Jimmy Reed. In 1976, Willie Dixon hired him to play in the Chicago Blues All-Stars. Campbell’s debut album, King of the Jungle, featuring Carey Bell on harmonica and Lafayette Leake on piano, was released the next year.

In 1984, Campbell left Chicago for Europe, living first in the Netherlands and later in Duisburg, Germany, where he remained for ten years before returning to Chicago.

Campbell’s last album was Spider Eating Preacher (Delmark, 2012). It was nominated for a Blues Music Award in 2013 in the category Traditional Blues Album.

In February 2013, Campbell suffered a stroke and a heart attack while on tour in Germany, leaving him paralyzed on the right side of his body. His wife, Barbara Basu, started the Eddie C. Campbell Assistance Fund to raise money to fly him back to Chicago for further medical treatment. He died in Chicago on November 20, 2018, aged 79.