South regional police say the driver of the school van was heading westbound on York Road, Route 116, in Heidelberg Township, York county.
The driver of the van then passed into the eastbound lane where it collided with a tractor trailer near the 6500 block of York Road.
Police say the driver of the van was killed immediately upon impact.
No children were in the school van and the driver of the tractor trailer was not injured.
Police are still working to identify the driver and notify family.
They say York Road will remain closed until investigators can determine why the driver swerved into the eastbound lane and exactly what caused the crash.
Crews are also making sure no hazardous materials leaked onto the road.
Police say the inclement weather was not a factor.