James never knew her father and was frequently neglected by her mother who pursued relationships with various men, according to Wikipedia. She began singing at age 5 in a church choir directed by James Earle Hines. She was raised by caregivers, one of whom would awaken her from sleep and beat her to sing on demand for his friends. She moved with her mother to San Francisco when she was 12 and within a few years she encountered musician Johnny Otis who helped secure her a record deal and shortened her name from Jamesetta to ''Etta." She dated B.B.King, whom she once said wrote the song Sweet Sixteen about her.

James was most famous for her goosebump-raising renditions of At Last, as well as Stormy Weather, both recorded on her 1961 album.

James' singing career declined in the late 70s as she wrestled with legal problems that stemmed for a heroin addiction for which she was in and out of treatment centers. But she returned to public in the late 80s with a performance in the documentary Hail! Hail! Rock 'n' Roll, released the album The Seven Year Itch and opened for the Rolling Stones in Montreal. Rolling Stone ranked her number 22 on their 100 Greatest Singers of All Time list. She was portrayed by Beyoncé Knowles in the movie Cadillac Records, but took offense when the R&B singer was invited to perform her signature hit At Last at President Obama's inauguration ball.

At the time of her death, she was the recipient of more than 30 awards from eight different organizations since 1989.

She died in Riverside, Calif. and is survived by her husband, Artis Mills, and two sons, Donto and Sametto.