Heavy snow and howling winds upended holiday plans at one of the busiest times of the year, as a huge cold front swept down from the Arctic and took freezing hold of the middle of the country.
Tens of millions of people were under winter storm advisories or warnings, with meteorologists saying it was so cold in places that anyone venturing outside risked frostbite within minutes.
"This is not like a snow day when you were a kid," President Joe Biden told reporters. "This is serious stuff."
Blinding whiteouts and hazardous road conditions were already spreading, even as 100 million people were expected to take to the roads, according to the American Automobile Association.
The I-90, a major highway running across the north was shuttered in South Dakota, with officials saying it would not reopen until Friday.
"Crews are using all available resources from across the state to clean up and restore travel," the South Dakota Department of Transport said.
"Multiple highways are currently listed as 'Road Impassable'... travel on the road segment is physically impossible due to widespread deep snow and drifts."
Around 100 motorists were stranded near Rapid City in the state, Pennington County Sheriff's Office tweeted.
"NO TRAVEL advised," it added.
Plane tracking website Flightaware.com showed more than 22,000 flights had been delayed on Thursday, with 5,500 cancelled outright, many at Chicago O'Hare or Denver, both international hubs.
Madison Painter told CNN she and her fiance had decided to drive 700 miles (1,100 kilometers) after their flight from Chicago to Atlanta had been cancelled.
"I wanted to get home to our families," she said.
Holiday travel volumes are expected to be close to pre-pandemic levels, with the busiest day on Thursday, three days before Christmas.