At least eight people have been killed in several states as a result of the Arctic weather.
Temperatures fell to -30C (-22F) in Chicago – colder than parts of Antarctica – and -37C in North Dakota.
Freezing weather will chill 250 million Americans, and 90 million will experience -17C (0F) or below.
What’s the forecast?
Snow fell throughout Wednesday, from the Great Lakes region into New England; as much as 24in (60cm) was forecast in the state of Wisconsin, and 6in in Illinois.
States of emergency have been declared in the Midwestern states of Wisconsin, Michigan and Illinois, and even in the normally warmer Deep South states of Alabama and Mississippi.
“This could possibly be history-making,” said Ricky Castro, a National Weather Service (NWS) meteorologist in Illinois.
Dangerous wind chills across the Upper Midwest and into the Ohio Valley were expected to last through Thursday, with heavy snow downwind of the Great Lakes, the NWS said.
Heavy rain and mountain snow were expected in the west of the country by the weekend, it added.
The NWS is warning frostbite is possible within just 10 minutes of being outside in such extreme temperatures.
Grand Forks, North Dakota, has seen the lowest wind chill so far at -54C on Wednesday morning.
Twenty million people in the continental US are expected to experience temperatures of -28C or lower by the week’s end.
How did the fatalities occur?
On Wednesday, two Michigan residents were found dead in their neighbourhoods, the Associated Press reported. Officials say one may have become disoriented and wandered into the cold without proper attire.
On Tuesday, a 55-year-old man froze to death in a Milwaukee, Wisconsin, garage, with the medical examiner’s office ruling he “apparently collapsed after shovelling snow”, local media reported.
In Pekin, Illinois, NBC News reported an 82-year-old man died from hypothermia outside his home.
A 75-year-old man was killed by a snow plough near Chicago on Monday. The driver of the plough has been placed on paid leave while the incident is investigated, according to WGN9 News.
In northern Indiana, a young couple died after a collision on icy roads.
And a University of Iowa student was found behind an academic hall several hours before dawn on Wednesday, reports say.
How is the cold snap affecting daily life?
The US Postal Service has called a halt to mail deliveries in parts of 10 states in the Great Plains and Midwest.
Hundreds of schools, as well as colleges and universities, have been closed in the affected states.
Beer deliveries in Wisconsin have been hit, too, as brewers delay shipments for fear their beverages will freeze in the trucks.
Weather officials in the state of Iowa have warned people to “avoid taking deep breaths, and to minimise talking” if they go outside.
Farmers across the Midwest have been taking measures to protect their livestock, including building igloos for chickens.
In North Dakota, cattle ranchers Joey Myers and Scott Bailey told Reuters news agency they planned on staying up with their animals during the cold snap to prevent fatalities.
Frigid weather could cause pregnant cows to deliver prematurely, the farmers said, and newborn calves cannot survive such conditions.
Animal rights organisation Peta has warned people to bring pets indoors.
Meanwhile, police in the Illinois county of McLean had some fun, announcing that Elsa from the Disney movie Frozen had been arrested.
What about Chicago?
Residents of America’s third largest city are no strangers to perishing cold, but they have been warned to expect an unusually dangerous freeze.
Chicago has seen more than 1,500 flights cancelled from its two main airports, and rail operator Amtrak has scrapped train services from its hub there.
With the icy breeze whipping off Lake Michigan, the Windy City will feel more like -45C.
Chicago mayor Rahm Emanuel urged people not to go outside if possible.
Dozens of “warming centres” have been opened for the estimated 80,000 rough sleepers there.
But at least one homeless Chicago man said he preferred to take his chances outdoors.
Tony Neeley told the New York Times: “A lot of us don’t go to the shelters because of bedbugs. We don’t go because people steal from you.
“We don’t go because you can’t even really sleep in the shelter.”
The Illinois city’s landmarks, including the Lincoln Park Zoo, Field Museum and Art Institute, are all shut.
A number of coffee shops and other local businesses have closed, including even some of its famous deep-dish pizza parlours.
Chicago police say people are being robbed at gunpoint of their coats, especially Canada Goose jackets, which can cost $1,100 (£900).