The National Weather Service said in its forecast discussion the storm system is bringing snow from the Central Plains, with the "most significant" snow to be expected across the Central Appalachians and into the Northeast.
"The snow will expand into the Northeast by Sunday evening and continue over the region through Monday evening," the agency said.
Winter weather advisories and winter storm warnings stretch from northern Texas all the way through Maine as the system crosses the country.
"It's a quick-moving storm, so the snowfall totals won't be huge but they might be huge-er across the Northeast than we've seen at any point this year," Fox News Chief Meteorologist Rick Reichmuth said on "Fox & Friends."
The greater New York City area should see between 4 to 8 inches of snow, with similar totals stretching up to Boston, according to Reichmuth.
Most of the heaviest snow will fall overnight, but the effects are expected to linger into the start of the week.
"The snow will be out of here by tomorrow but tomorrow morning's commute across parts of the Northeast will be tough," he said.
Snow was falling across Missouri on Sunday morning, creating travel headaches as between 2 and 4 inches of snow fell, FOX2 reported.
The Missouri State Highway Patrol said that a crash involving a semi-truck closed westbound Interstate 44 in Franklin County. The agency posted photos to Twitter of the truck crash on the snow-covered road.
"Drive slow and drive safe if you are traveling," the agency said.
Once the storm system moves out, another arctic blast of air is expected across the Midwest and the Northeast that will keep the snow around, according to Reichmuth. Parts of Montana, North and South Dakota were issued wind chill warnings with wind chills as low as minus-35 degrees expected through Monday morning.
The bitter cold is expected to last through Friday.
"It will be a really cold week," he said.