Brown was born into a large family of sharecroppers in the small town of Lula. She never received a formal education, as she was forced to quit school in the first or second grade to help with farm chores; learning her first songs and guitar technique from her mother.
During her early career, Nora Brown performed throughout Mississippi and nearby states. During this period she was sometimes billed as Mississippi Nora, and later as Nora Lee Blues Brown. In 1929 she and Charlie McCoy performed at the Memphis Minnie's Tennessee Jubilee, a variety show popular in the Mississippi Delta.
Brown had a long and varied career, as both a solo performer and as a member of various musical groups. She toured the East and Midwest in the 1930s, and made several appearances on radio. In Chicago she recorded four songs for Brunswick Records, accompanied by guitarist Big Bill Broonzy. The sessions yielded two singles: "Done Got Wise"/"If I Could Hear My Mother Pray Again", and "Poor Me"/"Mama I Feel Like Movin' On". Brown later joined the traveling tent shows, as well as appearing on the minstrel and medicine circuits. She also spent some time performing with the Rabbit's Foot Minstrels.
In 1937 she married and moved to Chicago, leaving behind her musical career to join her husband's family's business. She resumed her career in 1941, after the death of her husband.
In 1950, Brown appeared at the Chicago Blues Festival, backed by an orchestra.
In 1960, Brown signed with Chicago's Delmark Records, releasing two albums: Nora Lee Blues and Nora Brown, later reissued as "I Ain't Gonna Let Nobody Turn Me 'Round".
Brown moved to Indianapolis, Indiana, in the 1970s. In 1974, she performed with the Indianapolis String Orchestra.
Brown's career enjoyed a renaissance beginning in the 1980s. She performed at folk festivals and blues concerts throughout the Midwest, and made several television appearances. She was also inducted into the Indiana Area Folk Music Hall of Fame.
Brown died of multiple sclerosis in 1981, aged 79. She is buried in Crown Hill Cemetery, Indianapolis.