Lucille Hegamin nee Nelson was born in Macon, Georgia, in 1894. By the age of 15 she was touring the US Southern States with the Laurel Harper Minstrel Stock Company, billed as "The Georgia Peach". Whilst still a teenager she joined the migration north to Chicago where she worked with Tony Jackson and Jelly Roll Morton  working at cabarets and nightclubs. Aged 20, she teamed with pianist Bill Hegamin and whom she soon married. They moved to Los Angeles, California in 1918, and then to New York City the following year. In New York she continued her career as a cabaret and nightclub singer and performed in musical revues. In 1920, she and her husband formed the Blue Flame Syncopators who supported her as she toured the vaudeville circuit throughout Pennsylvania, West Virginia and Ohio.

In 1920 Lucille Hegamin became the second African-American Blues singer to release a record in 1920, just few months after Mamie Smith's groundbreaking success with "Crazy Blues". Hegamin's first record was "The Jazz Me Blues" and "Everybody's Blues" for Arto Records. It sold reasonably well but her next record in 1921 "Arkansas Blues" and "I'll Be Good But I'll Be Lonesome" was a big hit and made her a star of the emerging blues scene. When Arto went bankrupt in 1923, for the next three years Hegamin recorded for Cameo Records, becoming known as "The Cameo Girl".  Like Mamie Smith, Hegamin sang in a lighter, more urban and sophisticated style than the rougher rural-style blues singers such as Ma Rainey and Bessie Smith who became more popular a few years later.

Between 1926 and 1934 Lucille Hegamin performed in various Reviews in New York and Atlantic City, had her own radio show for a while, and continued to record. She made a decision to retire from the music business in 1934 and became a Registered Nurse, a profession she followed for the next 25 years, although she performed occasionally on a part time basis. Renewed interest in blues and folk persuaded her to come out of retirement in the early 1960's to make further recordings for Victoria Spivey's label, Spivey Records. She became increasingly frail during the late 1960's and she died in New York City in 1970 aged 75 years.