Tornadoes killed at least two people Monday in Alabama, caused serious damage in Mississippi and took aim at southern Tennessee, where forecasters warned that powerful twisters could wreak "complete devastation."
It was the followup punch delivered by the same weather system that killed at least 16 people Sunday in Arkansas, Oklahoma and Iowa.
Heavy damage was reported after a tornado touched down Monday afternoon in Limestone County in northern Alabama, the county Emergency Management Agency told NBC News. At least two people were killed in the town of Athens, Holly Hollman, a spokeswoman for the city, told NBC News.
The National Weather Service said the "large, violent" twister directly hit the Clements Fire Department shortly after 5 p.m. (6 p.m. ET). The two victims were believed to have been in a mobile home park that was devastated.
At midnight ET, a "supercell" storm system likely to spawn tornadoes was heading toward Birmingham and Jefferson County, the National Weather Service said.
Tornado warnings lighted up the weather map in red Monday night in counties from eastern Mississippi across northern Alabama and into southeastern Tennessee as far east as metro Chattanooga.
About 9:30 p.m. ET, a major tornado touched down in Lincoln County, Tenn., near the Alabama line, the National Weather Service reported. It said the twister, which was tossing debris thousands of feet in the air, was expected to cause "catastrophic damage" in parts of Lincoln and close-by Franklin and Moore counties.
Solid damage reports were hard to come by as drenching rains closed roadways to the area under more than 6 inches of water. But the weather service projected that "complete devastation" was likely.
County emergency management officials told NBC station WSMV of Nashville that South Lincoln Elementary School sustained significant damage and could be a total loss.
It was all part of the same weather system, one that that left severe damage across central Mississippi earlier in the day.
Mississippi Gov. Phil Bryant said the hardest-hit areas were Tupelo and Winston County near the town of Louisville.
"We're very fortunate that we have no reports of deaths in our city," Tupelo Mayor Jason Shelton said shortly after a strong tornado touched down and tracked northward. North Mississippi Medical Center treated 24 people, 20 of whom had been released, the hospital told NBC News.
"Please say a prayer for all those affected and our law enforcement officials," Shelton said.
NBC station WTVA reported that the worst damage in Tupelo was near Barnes Crossing Mall a couple of miles north of downtown. Managers said the mall itself wasn't hit, but Tupelo police told NBC News at least six other area businesses were rendered "structurally unsound."
WTVA was live on the air and had to be evacuated when the tornado — described by the National Weather Service as "large and violent" — hit the ground, leaving viewers to watch the news team scramble off their screens.
A tornado near Louisville extensively damaged Winston County Community Hospital and injured an undetermined number of people, said Temika Triplett, a spokeswoman for the Winston County Emergency Management Agency.
And it isn't over, said Greg Forbes, a severe weather expert for The Weather Channel. As the system moves eastward into Georgia, Florida and the Carolinas, Tuesday "looks very much like today," he said.
The system was moving very slowly, Forbes said, and it wasn't expected to reach Atlanta, the South's biggest city, until the worst time possible — the Tuesday morning rush hour.
An even broader swath of the middle of the country was at risk for some form of severe weather, as far north as Iowa, as far south as New Orleans and as far east as Charlotte, N.C. A jetliner flying the Memphis Grizzlies from Tennessee to Oklahoma City for an NBA playoff game was diverted to Tulsa because of the treacherous weather, the team said.
Besides twisters, the system was also packing heavy rain and hail, and the National Weather Service issued flash flood watches and warnings across much the South. Mississippi, Alabama, Tennessee and Georgia were under emergency declarations Monday night.
Susan Kroll, Erin McClam, Terry Pickard, Melinda Ryan and Edgar Zuniga Jr. of NBC News contributed to this report.