Shirley was born in Gluckstadt, Mississippi. He was Chairman of the Board for the Jackson Medical Mall Foundation, and an associate professor in pediatrics at the University of Mississippi Medical Center.
He was a graduate of Tougaloo College and Meharry Medical College. For a long time, Shirley was the only black pediatrician in the state of Mississippi. He was not dedicated to non-violence; upon hearing that the Ku Klux Klan was heading to his home, he warned the local police that his sons knew how to shoot. He also was known for installing wells to provide clean drinking water and for traveling the countryside to care for sick babies.
He was married to Ollye Shirley; they had four children.
In 2010, Shirley founded the HealthConnect program. Modeled after a similar program in Iran, the program sends doctors and nurses to poor rural homes to help prevent unnecessary ER visits.
- 2009 Governor's Initiative for Volunteer Excellence Award
- 2007 Mississippi Majesty Honoree 
- 1993 MacArthur Fellows Program
- Honoring Dr. Aaron Shirley For His Commitment To Service To The Cause of Health Care
- John D. and Catherine T. MacArthur Foundation (1997). The MacArthur Fellows Program: the first fifteen years, 1981-1996. John D. and Catherine T. MacArthur Foundation. p. 194. Retrieved 28 July 2012.
- Suzy Hansen (July 27, 2012). "What Can Mississippi Learn From Iran?". New York Times Magazine.
- Local Civil Rights Pioneer Dr. Aaron Shirley Dies
- "Dr. Blair Batson on Dr. Aaron Shirley's arrival at UMC", Winter Institute