The fatal accident happened around 3:30 a.m. Sunday along I-95 southbound on the bridge above Kerlin Street in Chester.
Police say the driver of Nissan Sentra lost control when the vehicle hit the guardrail, crossed three lanes of traffic, and then hit a concrete barrier.
A tractor-trailer then struck the Sentra.
Officials say the driver of the Sentra was killed.
The name of the victim has not been released.
While the highway was shut down due to the accident, traffic was being detoured onto Route 476.