Forecasters said snow, sleet and freezing rain, accompanied by dangerously frigid temperatures, would sweep the eastern two-thirds of the nation on Sunday and into next week.
Calling the storms "historic," President Donald Trump on Saturday approved federal emergency disaster declarations in South Carolina, Virginia, Tennessee, Georgia, North Carolina, Maryland, Arkansas, Kentucky, Louisiana, Mississippi, Indiana, and West Virginia.
"We will continue to monitor, and stay in touch with all States in the path of this storm. Stay Safe, and Stay Warm," Trump wrote in a post on Truth Social.
Seventeen states and the District of Columbia have declared weather emergencies, the Department of Homeland Security said.
"We do have tens of thousands of people in affected states in the South that have lost power. We have utility crews that are working to restore that as quick as possible," DHS Secretary Kristi Noem said late on Saturday.
The number of power outages continued to rise. More than 130,000 customers had lost electricity, the bulk of them in Texas and Louisiana, according to PowerOutage.com.
The US National Weather Service warned of an unusually expansive and long-duration winter storm that will bring widespread, heavy ice accumulation in the southeast US and cited "crippling to locally catastrophic impacts".
Weather service forecasters predicted record cold temperatures and dangerously cold wind chills descending further into the Great Plains region of the US by Monday.
More than 4000 US flights scheduled for Saturday had been cancelled, according to flight tracking website FlightAware. More than 9000 US flights originally set for Sunday also have been cancelled, the website indicated.
Major US airlines warned passengers to stay alert for abrupt flight changes and cancellations. In an update on its website on Saturday.
The airline said it was relocating experts from cold weather hubs to support de-icing and baggage teams at several southern airports.
JetBlue said as of Saturday morning it had cancelled about 1000 flights through Monday, with additional cancellations possible, as it was "closely monitoring" forecasts for the storm. US electric grid operators on Saturday stepped up precautions to avoid rotating blackouts.
Dominion Energy, whose Virginia operations include the largest collection of data centres in the world, said if its ice forecast holds, it could be among the largest-ever winter events to affect the utility's operations.
Noem warned Americans to take precautions.
"It's going to be very, very cold," Noem said.
"So we'd encourage everybody to stock up on fuel, stock up on food, and we will get through this together."