The National Weather Service also reported severe weather or damage Wednesday in Texas, Mississippi and Alabama. Tornadoes were confirmed in Marion County, Ky., and Harrison County, Ind.
In the mountains of North Carolina, iReporter Matt Able said most of the roads around Appalachian State in Boone were impassible because of flooding. He sent in video of people driving down U.S. 321, which was under several inches of water.
"People were driving down the middle of the (four-lane) road to avoid being swept away by the fast-moving water," he said.
CNN meteorologist Chad Myers said the massive storm system was 1,000 miles north to south, moving eastward in a belt that will eventually stretch from New York to Florida.
"If it's hot and humid where you are, then you are still in the danger zone," Myers said.
The strong cold front causing the severe weather brought huge extremes in temperature readings. Thermometers reached the low 80s in parts of southeast Georgia and South Carolina, the 50s in Tennessee and the 30s in Illinois.
Earlier, in Alabama, the storms blew the metal roof off a building in Sheffield, CNN affiliate WHNT said. The storm also damaged a church steeple in Rogersville, the station reported.
In Kentucky, winds blew off much of the roof of the Penrod Missionary Baptist Church and damaged several homes, CNN affiliate WFIE reported.
In Nashville, the weather service listed dozens of damage reports across the region: a funnel cloud was reported early Wednesday in Jackson County, there were dozens of reports of downed trees and power lines, and law enforcement reported damage to homes and businesses.
CNN affiliate WSMV also reported the partial collapse of an office building in Mount Juliet, Tennessee.
"I built it myself to take an event like this. And it looks like a freight train hit it," the station quoted building owner Dewey Lineberry as saying. "It's just destroyed. It laid the building down on top of cars, it put the building on top of people. It's unbelievable."
Workers who were inside the building when the storm hit took cover under mattresses, the station said.
The storm came dangerously close to WSMV, the station reported: Workers had to move to a safe room when a buzzer in the newsroom alerted them of storm danger around 4 a.m. Wednesday, the station reported.
CNN iReporter Matt Davis said overnight storms damaged a historic brick structure on Fairvue Plantation in Gallatin, Tenn.
"The plantation was a horse farm. Those (structures) have been standing there for 100 to 200 years. It was sad to see those collapsed and caved in. It's historic to the neighborhood," the high school student said.
On Tuesday, the storms raked Arkansas, Louisiana and Mississippi, among other places, with heavy rain and high wind.