Forecasters were predicting everything from freezing rain and snow in the north to torrential rain in the Ohio Valley and Appalachia and possibly even tornadoes in the South.
The worst of the storm was expected to hit Midwest population centers on Saturday, though the weather took a toll on air travel Friday with significant delays from Albuquerque to Denver to Chicago.
The foul weather could cause headaches for the estimated 94.5 million Americans planning to travel by road or air during this holiday season, which runs from Saturday through New Year's Day.
Most of the precipitation on Friday night was in the Texas panhandle, Oklahoma and southern Missouri. The system was expected to move north into the Chicago area late Saturday into Sunday as it crawls toward the northeast U.S. and Canada, National Weather Service meteorologist Mark Ratzer said.
But that may just be the pregame show; On Sunday, the rain is expected to turn to snow in some parts of the upper Midwest, with 6-8 inches north and west of Chicago and into Wisconsin, he said.
Dennis Richmond, 72, was worried about a possible delay to his son's Saturday flight from Washington, D.C., to Madison, Wis., which could get up to 8 inches of snow. He said he didn't tell his son to change his itinerary, though, because there were few alternatives, and that he still planned to drive the roughly 140 miles from La Crosse to pick him up.
"The thing is, trying to book another flight at this time of year is next to impossible," he said. "I just want to alert him to the fact he might be delayed."
Icy weather snarled traffic in Oklahoma on Friday. Police in Oklahoma City blamed at least one traffic death on the weather. Forecasters said up to a half-inch of ice could accumulate across the middle of the state, from the Texas border in the southwest to the Missouri border in the northeast.
In Wisconsin and Michigan, slippery roads from freezing rain forced some schools to cancel classes. A woman sleeping in a hotel in Holland in western Michigan was injured when a motorist lost control of his car on an icy street early Friday and slammed into the wall outside her room, MLive.com reported.
In New England, communities were planning for a bit of everything - snow, sleet and rain - but were most concerned about the threat of freezing rain.
The National Weather Service predicted that parts of Maine could get more than a half-inch coating of ice, which would make roads treacherous and cause widespread power outages.
"The best advice for everyone is just to really pay attention. With every few hours, we're going to get better information," Maine Emergency Management Agency spokeswoman Lynnette Miller said Friday.
An ice storm warning was issued until 6 a.m. Sunday by the National Weather Service for central and southwestern Oklahoma and until 6 p.m. Saturday for the northeastern portion of the state.
The 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.
In Indiana, the National Weather Service posted flood warnings along southern and central Indiana streams and predicted the highest flood crests along the East Fork of the White River since April 2011.
While the Midwest and Plains were preparing for ice and snow, residents down South were concerned about tornadoes, which forecasters said were possible this weekend even though they are uncommon this time of year. The area most threatened stretched from central and northeastern Texas through Louisiana, Mississippi, Arkansas and southeast Missouri, where 80 mph wind gusts and flash flooding were possible.
Tom Kines, an AccuWeather meteorologist, said a northern cold front clashing with warm, humid air from the South is causing the unsettled weather.
"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."
Weekend temperatures could surpass 70 degrees in Nashville this weekend and approach that in New York City as well, Kines said. But by Sunday night, the storm will be hammering the Northeast, where residents could be treated to a rare winter thunderstorm.
Kansas City, Mo., was bracing for freezing rain this weekend followed by 6 inches of snow.
If there is a silver lining, it's that Christmas happens mid-week this year, AAA spokeswoman Heather Hunter said.
"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.