It happened around 8 a.m. Wednesday on Lynch Store Road, about a half mile west of Doc Corbett Road in Cedar Grove.
Authorities said a blue Chevy Malibu was going north down Lynch Store Road, when it crossed the center line and struck a yellow Jeep in the southbound lane head-on.
Both vehicles were severely damaged in the crash, causing the drivers to be pinned inside.
The driver of the Malibu, 30-year-old Sean Austin of Roxboro, was taken to Duke Hospital where he later died.
The driver of the Jeep, 45-year-old Keith Howerton of Roxboro, was also taken to Duke Hospital with injuries to his ankles. No one else was injured.
Authorities said both drivers were wearing their seat belts, and alcohol was not a factor in the crash.
Lynch Store Road was shut down for a period of time as authorities worked to clear the scene.