Elizabeth Cotten started playing her older brother's banjo at eight years old and soon after began playing his guitar as well. Completely self taught, she played her guitar left-handed and upside-down, causing her to play the bass lines with her fingers and the melody with her thumb. This style of playing became what is known as “cotton picking” or alternate-picking style of playing.

Elizabeth Cotten began doing domestic work at age twelve, which was what her mother had done. She was married young, at the age of fifteen, to Frank Cotten and they had one daughter, Lillie. In 1940, she divorced Frank and moved in with her daughter Lillie and her husband. Cotten completely retired from guitar playing for twenty-five years, except for occasional church performances. It wasn't until she was in her sixties that she began recording and performing publicly.

Elizabeth Cotten was discovered in her sixties by the pioneering folk-singing Seeger family while she was working for them as a housekeeper. Her first recording, Negro Folk Songs and Tunes (later reissued as Freight Train and Other North Carolina Folk Songs) was produced by Mike Seeger in 1958 and is considered one of the greatest folk albums ever recorded.

In 1984, Cotten received a Grammy Award for Elizabeth Cotten Live!, recorded when she was ninety years old, as well as a National Heritage Fellowship. In 1989, Cotten was one of seventy-five influential African-American women chosen to be included in the photo documentary I Dream a World. Elizabeth Cotten died on June 29, 1987, at age of ninety-two in Syracuse, New York.