The storm was hitting much of the central US with blizzard conditions as of Saturday afternoon before it will make its way to the Northeast by Sunday.
Blizzard conditions on early Saturday were already buffeting the High Plains. A number of travel advisories have been issued.
Greeley, Colo., officials canceled the city's annual Greeley Lights the Night festival because of the weather.
Farther south, rain and thunderstorms were forecast along and ahead of the cold front, with heavy rainfall possible on Saturday in parts of the Tennessee and Ohio Valleys.
The rain will potentially change back into snow Monday afternoon into evening in the NYC and NJ metro area, before ending Tuesday morning.
Airlines at O'Hare International and Midway International airports in Chicago reported average delays of 15 minutes as a winter storm headed toward the Midwest with heavy snow and ice and gusty winds.
According to FlightAware, more than 225 USA flights had been canceled and more than 2,000 delayed on Saturday alone as of early afternoon.
About 49 million people are also expected to have traveled by auto for the Thanksgiving holiday, according to an estimate by AAA. "Everybody thinks the day before Thanksgiving is the busiest; it is not".
A major winter storm continues to make its way across the U.S.
Strong winds, heavy rain and strong thunderstorm are impacting some areas, as well, making travel extremely risky through the holiday weekend.
In Missouri, officials say three people were killed Saturday when their vehicles were swept off flooded roads in Bollinger County. The sheriff's office didn't provide the second child's age and gender.
In Arizona on Saturday, two children and two adults who were in a vehicle that had been swept away on Friday were rescued from a small island and the bank of the creek in Tonto National Forest north-east of Phoenix. Wells College is also closed Monday.
The heaviest of the anticipated winter weather, including snow or ice, will generally be north of Interstate 80, which stretches east and west in the upper third of the country, while the heaviest snow accumulation will be the eight to 16 inches that could fall on portions of Minnesota, the northern two-thirds of Wisconsin and upper Michigan, Hurley said. "Meanwhile, the Sierra Nevada could see snow measured in feet".
Wind gusts could reach up to 45 miles per hour in Tennessee and 50 miles per hour in North Carolina, the NWS says.
Almost the entire lengths of both Wyoming interstates were closed Saturday.
Travel was also hard in Colorado on Saturday as winds blew around snow that had fallen in previous days.