Thousands of flights were delayed or cancelled, and people across the region have been urged to stay off the roads, with plans to close some major highways in New York State.
Schools have also closed and homeless shelters are full to capacity.
The winter storm Hercules had dumped 21 inches of snow on Boxford, just north of Boston, by Thursday night, according to the National Weather Service.
Parts of upstate New York had 18 inches and between four and eight inches was forecast for New York City.
New York Governor Andrew Cuomo said: "People should definitely consider staying in their homes if the storm continues as we expect.
"This is nothing to be trifled with. We have learned too well over the past few years the power of Mother Nature. We have seen the damage that has been done."
More than 3,000 flights were cancelled across the country, according to Flightstats.com and nearly 10,000 delayed. At Chicago O'Hare airport alone, 842 flights were cancelled.
Waves crash against the seawall in Lynn, Massachusetts, during a snow storm
On Thursday night, the Weather Channel was reporting that at least 100 million Americans - across a 1,200 mile area stretching from Southern Indiana to Eastern Maine - were under some kind of winter storm warning.
Coastal flooding is forecast along low-lying parts of New England, with the risk greatest at high tide, near midnight.
The storm poses the first major challenge to the administration of New York's new mayor Bill de Blasio.
Problems caused by winter storms have been a political headache for mayors of America's biggest city for decades.
Mr de Blasio said: "We have to get it right. There is no question.
"Before I even think of politics or anything else, this is our job."
Some schools in New England and New York are staying closed as a precaution, and homeless shelters are expected to fill beyond capacity.
Before making its way to the northeast, the storm slammed the Midwest, forcing the cancellation of hundreds of flights.
Meanwhile, massive pile of salt used to clear icy roads fell on a worker in Philadelphia, crushing and killing him.
The 100-foot-tall pile of salt toppled over and trapped the man. Rescue crews could not save him.
