The southern cold snap is part of an arctic front that has put much of the Northeast and northern Plains under warnings and advisories for severe wind chills. Temperatures in parts of those regions could feel as cold as minus 30 Fahrenheit (minus 34 Celsius) on Tuesday, the National Weather Service said.
Georgia, Louisiana, Mississippi, North Carolina and South Carolina each declared a state of emergency, telling motorists to stay off the roads.
"Residents should not overreact but should make plans now to ensure they are prepared for prolonged freezing conditions and icy roadways," Mississippi Governor Phil Bryant said.
By Wednesday morning, the cold front is expected to blanket the Carolinas, Georgia and parts of Florida with a mix of freezing rain and sleet, according to the National Weather Service.
Forecasters say the front is moving slowly and the icy chill is not expected to leave the region until Thursday.
The last flight left New Orleans at about 11 a.m. local time (1700 GMT) on Tuesday and its Louis Armstrong International Airport was then closed to commercial traffic ahead of the storm. Authorities also shut the 24-mile (39-km) Causeway Bridge, which spans Lake Pontchartrain, because of icy conditions.
Residents and tourists excited by the novelty of the conditions took photos of icicles hanging from the wrought-iron balconies of the city's historic French Quarter.
Temperatures are forecast to hit a low of 23 degrees Fahrenheit (minus 5 Celsius) in New Orleans on Tuesday night and the city could see its first snowfall in years.
"This is pretty rare in New Orleans," Mike Efferson of the National Weather Service Office in Slidell, Louisiana, said of the conditions.
"This only happens about every 10 years."
Schools and government offices across a wide swath of the country were closed. Airlines canceled or delayed thousands of flights, and officials closed roads as conditions worsened.
North Carolina and South Carolina were expected to get the most snow, while the heaviest ice accumulation was forecast from Louisiana to the Carolinas, the weather service said.
Temperatures 10 to 20 degrees colder than normal were expected to continue for much of the eastern United States. In Washington, the National Gallery's skating rink was closed, with officials saying it was too cold for skaters to be out on the ice.
Jury selection in the corruption trial of a former New Orleans Mayor Ray Nagin was suspended because of the weather.
"We're getting a bit of everything," said Jody White, a police sergeant in Opelousas, Louisiana. "It's cold. The sleet is coming down in patches."
In Alabama, two people died and five others were hospitalized after a seven-car pileup on an ice-covered bridge near Montgomery, said Robyn Litchfield, an Alabama Department of Public Safety spokeswoman.
In Sandy Springs, near Atlanta, a baby was born in a car stuck in traffic caused by the storm. The baby and the mother were safe and healthy, police said.
The baby was delivered by the father and a Sandy Springs police officer.
Lawmakers in South Carolina canceled this week's session of the state legislature, citing weather concerns.
The storm took a toll on air travel across the region, with more than 3,000 U.S. flights canceled and hundreds of others delayed, according to flight tracking website FlightAware.com.
STOCKING UP ON SPIRITS
In Atlanta, 2 to 3 inches (5 to 8 cm) of snow caused massive traffic jams, auto accidents and road closures and schools and businesses closed by noon Tuesday.
The manager of a popular Louisiana grocery store said it was packed with shoppers stocking up on food and supplies before it also closed.
"They were buying hurricane stuff, including a lot of spirits, of course," said Edwin Moreno, manager at Dorignac's Food Center in suburban New Orleans where sales of alcoholic beverages soared.
The bad weather prompted a federal judge in Knoxville, Tennessee, to postpone court proceedings part way through a sentencing hearing for three peace activists, including an elderly nun.
Winter weather advisories were also issued for a wide swath of eastern and central Texas for Tuesday, with predictions of up to 1 inch (2.5 cm) of snow near the state's border with northern Louisiana.
Rain and freezing temperatures combined to snarl the morning commute through large parts of central Texas and Louisiana, where roads and bridges were iced over. Police in Austin, Texas, reported more than 150 crashes caused by icy roads but said there had been no fatalities.