The crash, on I-78 in Lebanon County – 75miles north-west of Philadelphia – left trucks and cars strewn across three lanes of traffic and the central reservation.
The Pennsylvania Emergency Management Agency said 40 people had been taken to hospital and 70 to a temporary shelter.
Drivers have been urged to use caution during the icy weather.
A spokeswoman for Penn State Hershey Medical Center said three patients had been brought in a critical condition, three more with moderate to severe injuries and four with minor injuries.
The accident happened at 9:30 a.m. at mile marker 7.5 and the interstate is shut down in both directions, state police said.
Agency spokesman Cory Angell said drifting snow had been reported in the area of the crash, which took place in strong winds on the eastern carriageway of Interstate 78 near Bethel Township.
“You could be driving down the interstate and all of a sudden conditions change because the winds are drifting the snow,” he said.
Witnesses described a scene of devastation with reports that some people remain trapped in vehicles.
“The snow just started and it was a total whiteout. The car in front of us just disappeared,” driver Ashley Fisher told NBC News.
“We were able to stop, but a couple cars slid and hit the shoulder. It was a mess.”
Officials have warned people in the north-eastern US to stay indoors during what the National Weather Service described as “life-threatening temperatures”.
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