AAA projected that nearly 95 million Americans would travel 50 miles or more during the holiday period, which runs from Saturday through Jan. 1.
Temperatures that hovered in the 60s in some parts of the Midwest on Thursday plummeted overnight, and freezing rain Friday morning snarled traffic and forced some school closures in Michigan and Wisconsin. The Wisconsin Department of Transportation said Interstate 90/94 was ice-covered from Tomah and Mauston. The state was bracing for significant snow, sleet and ice.
Although few flights had been cancelled by midday Friday, the weather was taking a toll on air travel: FlightStats.com reported more than 1,300 U.S. delays, with the most at Chicago's O'Hare, Denver International, and the three big New York-area airports.
The National Weather Service issued a flash flood watch from Arkansas northeastward through parts of Missouri, Illinois, Indiana and Ohio, with up to 4 inches of rain projected. With falling temperatures, some of that could be freezing rain by Saturday night in the St. Louis area, weather service meteorologist Jon Carney said.
"It's definitely a concern that there could be flooding," Carney said.
Forecasters said thunderstorms would likely develop in the South. The region most at peril is from central and northeastern Texas through Louisiana, Mississippi, Arkansas and southeast Missouri. Wind gusts could reach 80 mph, and flash flooding was possible.
By Sunday night, the storm systems will be hammering the East Coast. Some New England and mid-Atlantic states could see rare winter thunderstorms.
Tom Kines, an AccuWeather meteorologist, said the unsettled weather comes as a cold front in the northern U.S. clashes with unusually warm and humid air coming up from the South. He said that warm air will lead to record or near-record highs in many places over the next day or two. Nashville could reach into the 70s on Saturday. New York City could approach 70 degrees on Sunday.
The warm air, though, will bring plenty of trouble to some areas.
"I think there's a high likelihood there will be severe storms with hail and damaging wind" in parts of the South, Kines said. "Whether or not there's tornadoes, that's tough to say, but I will say the conditions are right."
Tornadoes are far more common in the spring and summer, but not unheard of in the winter. A tornado outbreak on Christmas Day 2012 reached from northeastern Texas through central Alabama one twister hit Mobile, Ala. A tornado on Dec. 16, 2000, killed 11 people in Tuscaloosa, Ala.
Farther north, more traditional winter weather was the biggest worry. Kansas City, Mo., was bracing for freezing rain, then 6 inches of snow. In New England, Nikki Becker of the National Weather Service said much of Maine and parts of New Hampshire could get up to a half-inch of ice Saturday night through Sunday morning.
The timing couldn't be worse. AAA is projecting record travel for this holiday period, and spokeswoman Heather Hunter said more than 90 percent of travelers will get there by car. She encouraged drivers to check the weather, not only at their destination but at points along the route, before heading out. Motorists should also make sure their vehicles are road trip-ready, especially the tread and air pressure on the tires. They should also make sure there is plenty of windshield washer fluid that won't freeze.
The good news is that Christmas is mid-week.
"When a holiday falls on a Wednesday it gives travelers more flexibility of either leaving the weekend before, or traveling right before the holiday and extending the trip through the following weekend," Hunter said.
AP Business Writer Joshua Freed in Minneapolis contributed to this report.