More than 65 million people in the affected areas are under winter weather alert, the National Weather Service said.
Heavy snowfall is expected early Sunday over parts of central and southern Appalachia and the mid-Atlantic region, the NWS reported.
Rain, snow, sleet and freezing rain – or a combination thereof – will make travel difficult over the three-day holiday weekend in affected areas.
On Friday, an 8 to 12 inch band of snow was recorded in parts of North Dakota.
From there, the system dipped further south, heading into Missouri, Arkansas and Kansas.
The Southeast can have a mix of everything
For much of the Southeast, this system will begin as rain on Saturday.
As temperatures drop, this rain turns to freezing rain, sleet and eventually snow in many places.
States of emergency were declared by the governors of Georgia, North Carolina, South Carolina and Virginia, allowing assets and resources to be positioned before the storm arrives.
Georgia Governor Brian Kemp ordered the state Department of Defense to prepare 1,000 National Guard troops to help respond to the storm.
In South Carolina, Governor Henry McMaster urged residents to monitor local weather forecasts and take precautions.
Predicting winter weather in the Southeast is never easy, as timing often comes down to the wire.
“These different types of winter precipitation are very sensitive to small changes,” said Kyle Thiem, meteorologist at the NWS office in Atlanta. “A change of just one or two degrees can mean the difference between relatively innocuous precipitation and hard-hitting accumulations of ice and snow.”
However, it is the slow forward speed of this system that provides the setup for a crippling ice storm that could knock out power to millions.
The Carolinas will be the region most likely to experience ice, with cities like Charlotte and Columbia potentially seeing up to half an inch of ice, which, with strong winds, will bring down trees and power lines.
An ice storm warning was issued for parts of South Carolina ahead of this system and is in effect Saturday evening through Sunday evening.
In the southern Appalachians, snow totals will increase as rapidly as elevation. Asheville, North Carolina, for example, should pick up 8 to 12 inches, but could reach 20 inches at elevations above 4,000 feet.
Mid-Atlantic and Northeast
The storm will turn to the East Coast on Sunday and Monday, with heavy snowfall of more than a foot expected in some places.
Some snow will fall in major metropolitan areas of Washington, DC, Philadelphia, New York and Boston, but a change in rain will keep the accumulations going.
Interior cities such as Charleston, Pittsburgh, Buffalo, Syracuse and Burlington, Vermont will see the heaviest snow.
What helps the northeast is that long before the main snowfall arrives, very cold air and dangerous wind chills will be in place.
Wind chill alerts are in effect for more than 20 million people on Friday and Saturday as temperatures feel like they could drop to 40 to 45 below freezing across much of the New England interior.
“Dangerously cold wind chills could cause frostbite to exposed skin in as little as 10 minutes,” the NWS warned.
CNN meteorologists Chad Myers, Dave Hennen, Monica Garrett and Haley Brink contributed to this story