Parts of the turnpike were closed as the crashes, involving about 100 vehicles, started about 8:25 a.m. EST with up to 15 vehicles smacking into each other in southern Bucks County near the New Jersey state line, CNN reported.
About 20 more wrecks happened over a stretch of several miles, spanning two counties, said Pat Ponticelli, Bensalem Township's deputy director of public safety.
At least three people were injured in the crashes. Authorities were still working to determine how many people were hurt.
Bill Capone, spokesman for Pennsylvania Turnpike Commission, expected it to be several hours before the wreckage would be cleared.
The crashes had not been specifically attributed to weather by authorities, but CNN affiliate KYW-TV, Philadelphia, said there was some freezing rain in the Philadelphia area.
NBC News reported upstate New York had received up to 27 inches and parts of Pennsylvania had 22.5 with forecasters calling for up to 6 more inches to fall on parts of the East Coast Saturday.
The network said the storm forced the cancellation of about 2,100 flights Friday after grounding more than 7,100 flights the day before, the worst-ever winter period for the nation's airlines.
More than 200,000 customers were without power Friday, mostly in South Carolina and Georgia, the network said, just a portion of the approximately 1.2 million who had been affected at some point by the storm.
At least 25 deaths were attributed to the storm across the nation since Monday, NBC said.
New York City received up to 11 inches of snow, and Fairfield, Conn., got 14 inches, CNN said.
Before the worst of the storm hit, N.J. Gov. Chris Christie said: "This has just been a brutal winter where it never really has gotten warmer. And so the natural melting away of snow and ice is not happening."