Born in Nashville, she was adopted by missionaries and raised in Kobe, Japan giving her exposure to multiple languages and cultures. Her first training was simple spiritual piano, but in her teens she moved to guitar, beginning a stage career in Atlanta, Georgia in the mid-1960s.
After a stint in New York City where she played with a young Jimi Hendrix and traded influences with him, she returned to Atlanta to form the band Fear Itself, a psychedelic-power band. After recording one album, McIlwaine went solo, recording two albums for Polydor, Honky Tonk Angel (1972; see 1972 in music) and We the People (1973; see 1973 in music), the latter featuring a hit single, "I Don't Want to Play".
McIlwain's career was irregular, plagued by conflict with her record producers who wanted to change her sound. Her most critically acclaimed album is The Real Ellen McIlwaine, recorded in Montréal in 1975 (see 1975 in music). A 1982 (see 1982 in music) project, Everybody Needs It, was also very successful, and featured bassist Jack Bruce. Since moving to Canada in 1987 (first Toronto, later Alberta), she has recorded for Stony Plain, which has also re-released her early vinyl material on CD. Her most recent CD Spontaneous Combustion features Taj Mahal and is on the German Tradition und Moderne label.