The driver in the vehicle that was struck, Jeffrey Mark Phillippe of Kennett Square, suffered severe injuries and died.
The accident happened around 5:15 a.m. Wednesday on the Route 1 (Baltimore Pike) near Creek Road.
Police tell Action News a vehicle in the southbound lanes lost control after traveling over ice and snow.
That vehicle then crossed into the northbound lanes, striking the vehicle Phillippe was driving.
The victims were taken by helicopter to an area hospital. But Phillippe died from his injuries.
Route 1 was closed, but has reopened in both directions.