According to the Fayette County Coroner, 37-year-old Jotham E. Barnette died in the crash.
Lexington Police said two cars collided head-on at Iron Works Pike near Newtown Pike.
Two people were taken to the hospital with life-threatening injuries. Two others were hospitalized with non-life-threatening injuries.
Barnette was pronounced dead at the hospital.
The cause of the crash is under investigation.
The area of Iron Works Pike was closed for several hours as police investigated the crash.