Police told ABC11 that it happened just before 9 p.m. when a Toyota driven by 59-year-old John Michael Williams, of Durham, was going southbound in the northbound lanes, and collided with another vehicle.
Williams was pronounced dead at the scene.
Williams' car collided head-on with a northbound Jeep driven by Jimmy Allen, 25, of Hillsborough. Allen and his brother, 30-year-old Walter Allen, suffered serious injuries and remain hospitalized. A back seat passenger in Allen's Jeep, 28-year-old Michael Carter, 28, of Durham, was treated and released.
Investigators are still trying to determine how Williams entered the highway in the wrong direction.
No charges have been filed.