The crash happened just after 5 a.m. Sunday in Prince William County.
Police say the two vehicles collided in the southbound lanes of Interstate 95 near mile marker 156 in the Woodbridge area.
The tractor-trailer struck an overpass support pillar, causing the trailer to rip open and the contents to spill onto the highway. The man behind the wheel of the truck died at the scene.
Authorities say that while the driver of the sedan was being treated by emergency crews at the scene, he fled the ambulance and ran from the scene.
The crash remains under investigation.