She attended public schools in her hometown, Minneapolis, Minnesota, and in Sioux Falls, South Dakota. In childhood, as she developed as a pianist, young Eileen was introduced to and became partial to the music of those she calls the "piano composers," including Johann Sebastian Bach, Ludwig van Beethoven, and Claude Debussy. In addition, her piano teachers, mostly white, were concerned that she would know music by black composers and introduced her to R. Nathaniel Dett's In the Bottoms, among other such compositions.
Southern majored in commercial art at Chicago's Lindblom High School. During the same period she won piano-performance and essay competitions, taught piano lessons, and directed musical activities at the Lincoln Community Center. She gave her first piano recital at the age of twelve and made her debut in Chicago Orchestra Hall at age eighteen, playing a Mozart concerto with the symphony orchestra of the Chicago Musical College.
She attended and received degrees from the University of Chicago (B.A., 1940, and M. A., 1941) and New York University (Ph.D., 1961). Her relationship with Cecil Smith encouraged her to further develop her interest in Negro folk music and he advised for her master's thesis.
Southern also studied piano privately at Chicago Musical College, the Juilliard School of Music, and Boston University. She was the first black woman to be appointed a tenured full professor at Harvard University. Her best known book is the seminal history The Music of Black Americans (1971). Her other work is Biographical Dictionary of Afro-American and African Musicians (1982). She founded The Black Perspective in Music in 1973, with her husband, Prof. Joseph Southern. It was the first musicological journal on the study of black music, and she was its editor until it ceased publication in 1990.
She also discovered Frank Johnson, a black Philadelphia bandleader who'd risen to fame at the end of the 1700s. He'd led Frank Johnson's Colored Band and by 1818 had taken his band as far south as Richmond, Virginia, playing dances for white southerners. Johnson had played a command performance at Buckingham Palace, where he received a silver bugle in appreciation.
Dr. Southern received a National Humanities Medal in 2001 for having "helped transform the study and understanding of American music." She also received a Lifetime Achievement Award from the Society of American Music in 2000.