The crash happened between the exits for Highway 264 and Poole Road.
Raleigh Police Department said it received a call about the crash at around 4:30 a.m. When officers arrived, they found the drivers of each vehicle suffering from serious injuries.
Both drivers were taken to the hospital for treatment.
A man who was driving one of the cars was later pronounced dead, Raleigh police said.
The female driver in the other vehicle was seriously injured but is expected to survive. There were no passengers in either of the vehicles.
The road was closed from around 4:30 a.m. until 7 a.m. Traffic had to be diverted onto Highway 87 to get around the closed section of road.