Hegemin was born a Lucille Nelson in Macon, Georgia. By the age of 15 she was touring the US South with Minstrel shows. She became a prominent singer, billed as "The Georgia Peach". She settled in Chicago, Illinois in 1914. where she worked with Tony Jackson and Jelly Roll Morton before marrying pianist Bill Hegamin.
The Hegamins moved to Los Angeles, California in 1918, then to New York City the following year. Bill Hegamin led his wife's accompanying band, called the Blue Flame Syncopators.
In August of 1920 Lucille Hegamin became the second African American blues singer to record, after Mamie Smith. Hegamin made a series of recordings for the Arto record label through 1922, then some sides for Paramount, and from 1922 through late 1926 recorded for Cameo Records. Like Mamie Smith, Hegamin sang in a lighter, more pop-tune influenced style than the rougher rural-style blues singers such as Ma Rainey and Bessie Smith who became more popular a few years later.
In 1926 Lucille Hegamin performed in Clarence Williams' Review at the Lincoln Theater in New York, then in various reviews in New York and Atlantic City, New Jersey through 1934.
In 1929 she had a radio show on WABC, New York.
In 1932 she recorded for Okeh Records.
About 1934 she retired from music as a profession, and worked as a nurse.
She came out of retirement to make more records in 1961 and 1962.
Lucille Hegamin died in New York City and was interred in the Cemetery of the Evergreens in Brooklyn, New York.