"Arctic air already in place across the central and eastern US will work in concert with this dynamic system to deliver a wide swath of more than a foot (30 centimeters) of heavy snow northward across the upper Ohio Valley through the lower Great Lakes," the NWS said.
The storm spawned damaging tornadoes in Florida and flooding in parts of the coast, while in the Carolinas and up through the Appalachians, icy conditions and blustery winds raised concerns.
In all, more than 80 million people fell under the winter weather alerts, US media reported.
Some 2,900 flights within, into or out of the US were canceled by mid-afternoon Sunday, according to the FlightAware website, and a further 2,400 were delayed.
About 235,000 customers had already lost power in the southeast, including more than 150,000 in the Carolinas, according to the website PowerOutage.US.
Georgia Governor Brian Kemp had declared a state of emergency on Friday, and snowplows were at work before noon to clear the roads.
Virginia and North Carolina have also declared states of emergency. The Weather Channel reported that more than a foot of snow had fallen in North Carolina.
The NWS even reported some snow flurries in Pensacola, Florida, while usually mild Atlanta, Georgia also saw snow.
The storm is expected to cause some coastal flooding, and the NWS warned that winds could near hurricane force on the Atlantic coast.
The northeastern United States had already seen snow chaos in early January, when a storm blanketed the Northeast.
After that storm, hundreds of motorists were stuck for more than 24 hours on a major highway linking to the capital Washington.