Over 2,000 flights have been canceled nationwide Friday as the Midwest is pummeled by snow and the South and Northeast brace for rough weather of their own.
The Midwest and the Great Lakes are facing blizzard warnings on Friday.
Whiteout conditions, heavy snow, wind gusts up to 50mph and low visibility will continue through rush hour Friday night from Iowa to the Great Lakes, including Chicago.
Days ahead of Monday's Iowa caucuses, the National Weather Service in Des Moines is urging drivers to stay off the roads.
The weather is also crippling travel by road and air in Illinois.
A ground stop was issued at Chicago O'Hare International Airport for part of Friday morning due to snow and ice.
Chicago O'Hare and Chicago Midway International Airport are seeing the highest number of cancellations in the U.S.
Six to 12 inches of snow is forecast for the Midwest through Saturday.
MORE: What every motorist needs to know about driving in snowIn the South, severe storms will be ongoing from Atlanta to Raleigh, North Carolina, on Friday night.
Damaging winds are expected and tornadoes are possible across the South.
The storm will move into the Northeast overnight, bringing up to 2 inches of heavy rain and winds up to 40 mph to Washington, D.C., New York City and Boston.
Rivers remain swollen in the Northeast from recent rainfall, so the incoming downpour will only prolong flooding issues. New Jersey's Passaic River reached its crest on Thursday night in the major flood stage. Flash flooding, river flooding and coastal flooding are all possible into the weekend across the Northeast.
MORE: Texas, Louisiana among states bracing for record cold: Latest forecastMoving in behind the storm is a major arctic blast that will bring brutally cold temperatures to millions this weekend and early next week.
Starting Saturday morning, the wind chill -- what temperature it feels like -- could plunge to minus 60 degrees in Montana and minus 40 degrees across the central and northern Plains.
In Kansas City on Saturday, when the Chiefs host the Miami Dolphins, the wind chill is forecast to be minus 23 degrees.
MORE: How to stay safe and prepare for freezing temperaturesIn New York, Gov. Kathy Hochul is warning "of potentially dangerous and life-threatening blizzard-like conditions" along Lake Erie and Lake Ontario on Saturday night and Sunday.
Some areas could get up to 1 foot of snow and residents should be prepared for freezing temperatures and possible power outages, the governor said.
Ahead of Sunday's playoff game, Hochul urged Buffalo Bills fans to "enjoy the game from home," adding, "however, if they are planning to attend the game, they should travel with extreme caution."
On Monday, the temperature will be bone-chilling across the Plains and Midwest. During the Iowa caucuses Monday, the wind chill will clock in at minus 25 degrees.
There's also the potential for snow and ice to develop in the South, from Texas to Tennessee, on Sunday and Monday.