By BBC News
A state of emergency has been declared in Kentucky, Virginia, Kansas, Arkansas and Missouri.
Conditions on roads have already deteriorated, with poor weather leading to crashes involving lorries and cars, as well as a fire truck rolling over in Kansas, according to state highway patrol trooper Ben Gardner.
Parts of the US unaccustomed to severe cold, including Mississippi and Florida, have been warned to expect treacherous conditions.
As the storm moves east, millions more Americans will see record-low temperatures, forecasters said.
A blizzard warning has been issued for portions of central, south-central, south-west, and west-central Kansas due the severe weather.
The NWS has urged people to delay all travel due to the “treacherous and potentially life-threatening” conditions.
Visibility may drop below 0.25 miles (0.4km) due to falling and blowing snow, with “whiteout conditions” expected, it adds.
Gusts of up to 45mph (72 kmh) and an additional 2in (5cm) of snowfall are expected.
The alert is effective immediately and lasts until 18:00 local time on Sunday (00:00 GMT on Monday).
More than 2,000 flights have been delayed and 1,500 cancelled in and out of the US today, according to tracking website FlightAware.
According to the live data, Kansas City International Airport is the worst affected for outbound flights, with 86% cancelled.
For inbound flights, St. Louis Lambert International Airport in Missouri tops the chart, with 53% of flights delayed and 7% cancelled as of 10:20 local time (16:20 GMT).
American Airlines has issued travel alerts for 46 airports due to the winter storm expected to sweep across the middle of the US and the east coast.
The alert covers airports in several states, from Kansas and Missouri, to Pennsylvania and New Jersey. The airline has published a full list of conditions for ticket changes.
American says it may be able to waive change fees for customers travelling to and from those airports because of the potential flight disruptions.
Delta, Southwest and United airlines have offered similar services to their customers.
As the storm moves east, cities like Washington DC and Philadelphia are bracing for the snow and wind.
Philadelphia’s mayor has announced the state is closing all its public schools and government offices on Monday because of the impending storm.
The city is expecting up to 7 inches of snow (18cm) and temperatures as low as -6C (21F), according to BBC Weather.
