The accident occurred just after 11:30 a.m. between Gulph Mills Road and Route 202.
Police say a tractor trailer was unable to stop and slammed into a row of vehicles, creating a chain-reaction crash.
Police only described the person killed as a male. The identity is being withheld pending notification of next-of-kin.
The coroner could be seen looking inside of a dark-colored vehicle that was partially underneath the trailer.
"We all went to try and help the guy out. He wasn't conscious and someone who was an EMS worker took his pulse and said they got a faint pulse," said witness Kevin McCloskey.
Three other people were injured in this crash. Chopper 6 HD was overhead as two victims were placed in waiting ambulances from a maroon-colored vehicle.
The tractor trailer driver was also taken to the hospital.
Ariel Froumy was among those involved in the crash. Her pickup truck suffered only minor damage thanks to her quick thinking.
"All I saw was the blue tractor trailer coming. I just tried to speed up and move to the side of the road. That's all I remember," Froumy said.
Crash experts have been on scene. The cause of the wreck is still under investigation.
"It is a fatality so, per law, a blood sample will be taken of that driver so we can find out, so we can make sure, there is no foul play or anything like that going on," said Trooper Danea Durham of the Pa. State Police. "We are not thinking about any kinds of charges right now."
The scene is just a few hundred yards from a new westbound off-ramp PennDOT opened about an hour before the wreck.
That ramp sends traffic onto South Gulph Road and South Henderson Road.