More than a dozen states are under a wind chill advisory or warning, according to the National Weather Service.
Wind chills of 25 to 45 degrees below zero are expected for parts of New England, CNN meteorologist Michael Guy said.
New York Mayor Bill de Blasio, in a news conference at the New York City Office of Emergency Management on Saturday morning, urged New Yorkers to take precautionary measures.
"The city is facing some of the coldest temperatures and wind chills we've seen in the last 20 years," de Blasio said.
Snow was a factor in a fatal pileup involving at least 60 vehicles on Interstate 78 near Fredericksburg, Pennsylvania.
Authorities didn't specify how many people were killed but said more than 70 were injured.
"It was definitely a whiteout, I couldn't see any further than probably two city blocks," Raoul Jardine of Allentown said. "I saw brake lights and pulled off to the side. Somebody hit me when I was parked in the shoulder."
Forecasters say a number of record low temperatures are expected Saturday night into Sunday morning for much of New England.
Near-zero temperatures are expected in New York's Central Park, while it is forecast to dip below zero in Boston.
Extreme temperatures even put the 2016 Ice Festival on ice. The Central Park event was canceled and will not be rescheduled "due to extreme temperatures and high winds," the Central Park Conservancy posted on Twitter.
"Extremely cold weather can be life-threatening -- especially for seniors, infants and people with medical conditions. We are urging residents to stay inside as much as possible, take care of yourselves and your neighbors, and wear multiple layers of warm clothing when outside," said de Blasio.
Mayor de Blasio also issued a citywide advisory to all property owners, construction sites and crane operators to take precautions; all crane operations were stopped Saturday because of the high winds.
Weather maps show a cold air mass across the Great Lakes triggering heavy lake-effect
snow that is pushing inland, especially near Buffalo, New York.
Lake-effect snow comes about as moisture from warmer lake waters mixes with cold air from the north, causing more than 2 to 3 inches of snow an hour.
"Depending on where you are, if you're just south or north of this lake effect, it can look like a wall of snow is coming down," said CNN meteorologist Chad Myers.
Forecasters predict as many as 18 cities in the East could see record lows Sunday.
This bone-chilling cold weather comes a little more than two weeks after a massive winter storm
pummeled New York and the Mid-Atlantic states with several feet of snow.
Elsewhere, another storm is expected to develop Monday in the Southeast and then move to the Northeast by Tuesday. The heaviest snow will likely fall from Tennessee to the interior Northeast, meteorologists say, especially near the eastern Great Lakes and higher elevations of the Appalachians.
The cold didn't put a damper on the annual Polar Bear Plunge on Saturday in Sea Isle City, New Jersey, Philly.com reported
. About 2,000 people went into the ocean despite temperatures of about 20 degrees.