Icy roads were blamed for the deaths of 14 people, mostly in Nebraska and Kansas. Some 100 flights leaving Minneapolis were cancelled.
The US weather service said the storm was spanning two-thirds of the country.
It advised against non-essential travel and scores of churches cancelled Christmas services.
Up to 2ft (60cm) of snow was possible in some areas by Christmas Day (Friday), forecasters said.
Scott Blair, a National Weather Service meteorologist in Topeka, Kansas, said the wind was becoming a serious issue in the central part of that state, with gusts reaching 40mph (64km/h).
"We're going to see blowing snow," he said. "The big concern comes later when we see snowfall with the wind, causing reduced visibility."
The US East Coast is still recovering from record snowfall last weekend, which brought much of the capital Washington DC to a standstill.
Tens of thousands of people in West Virginia and Virginia are still without power.
'Killer wind'
Blizzard warnings were issued for Iowa, Kansas, Minnesota, Missouri, Nebraska, North Dakota, Oklahoma, South Dakota, Texas and Wisconsin, and drivers were encouraged to pack emergency kits before setting out during what is normally one of the busiest travel periods of the year.
There's just a humongous storm moving across the centre of the country, basically from the Canadian border to Texas and spreading from west Colorado to Illinois," Pat Slattery, a spokesman for the National Weather Service, told AFP news agency.
"This is not a storm to be messed with."
He said freezing rain and high winds was making driving extremely dangerous.
"The wind is killer, especially when you're empty," trucker Jim Reed told The Associated Press during a stop in Omaha, Nebraska.
"Anything that's boxed, like a refrigerator trailer like I have, becomes like a giant sail in the wind."
More than 20 vehicles were involved in a pile-up on Interstate 40 in Midwest City, Oklahoma.
'Avoiding funerals'
The Rev Joseph Mirowski of the Greek Orthodox Church of the Transfiguration in Mason City, Iowa, cancelled his Christmas Eve service as the area braced itself for up to 1ft of snow.
"I don't think God wants anyone to get killed or break a hip or break a knee or something," he said.
At the Grace Memorial Episcopal Church in Wabasha, Minnesota, the Rev Roger Claxton cancelled his Christmas Eve service out of fear his congregation's senior citizens would feel compelled to attend.
"I'd rather have people stay home than do their funerals in a couple of weeks," he remarked.
Texas Governor Rick Perry activated military personnel to help drivers while North Dakota Governor John Hoeven placed additional state troopers and the National Guard on standby.
The latest storm began in the south-west on Tuesday, causing blizzard-like conditions and travel chaos, before spreading to the east and north.
Flooding was predicted across Texas and into the Ohio Valley.
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