The crash happened near the intersection of County Road 814 (Richmond Road) and County Road 1467.
Lee County Coroner Carolyn Green said the man killed was in one of the three cars in the crash and he was from the Fulton area. His name was not immediately released. Lee County Sheriff Jim Johnson said they do not believe he was wearing a seat belt and was trapped in the car.
Four others involved in the crash were transported to North Mississippi Medical Center.
The Lee County Sheriff's Department is investigating the crash.