In Arkansas and Mississippi, the hardest hit states, more than 23 people were killed and more than 200 injured over the last three days by tornadoes that reduced homes to splinters, snapped trees like twigs and lifted trucks into the air.
Deaths were also reported in Oklahoma and Iowa on Sunday, and Alabama and Tennessee on Monday.
Makeshift shelters have been set up for thousands of families forced out of their homes while the National Guard, local police and residents who had lost all their possessions sifted through the rubble looking for more victims.
"People were running around screaming, trying to find their kids. There was nothing left," Melba Reed said as she described the aftermath of a tornado in Louisville, Mississippi, a town of about 7,000 in the central part of the state.
A massive area home to tens of millions of people stretching across large parts of the South and into Pennsylvania and Ohio was under some threat from the storm system that spawned the tornadoes, forecasters said.
"We will see tornadoes again today and unfortunately, the areas that are under the gun today are the same ones that were under the gun yesterday," said Bill Bunting, operations chief at the National Weather Service's Storm Predictions Center in Norman, Oklahoma.
Southern and eastern Mississippi as well as central and western Alabama were under the highest threats for tornadoes, damaging winds and hail, he said.
Tens of thousands of customers along the path of the storm were without power on Tuesday morning, with the worst outages in parts of Alabama and Georgia, utility companies reported.
In western North Carolina, fire department personnel used boats to rescue people from homes and vehicles hit by flash floods during the night.
In Arkansas, residents of central Faulkner County, where most of the damage occurred, sorted through the rubble as they tried to piece their lives back together.
"There is joy because you find something that's not broken and then you find something that's shattered that meant a lot," said Terry Lee, whose home was damaged by a tornado.
The White House said President Barack Obama declared a major disaster in Arkansas and ordered federal aid to supplement state and local recovery efforts.
Some tornadoes registered an EF-3 on the Enhanced Fujita scale that measures strength, meaning they packed winds of about 150 mph (240 kph), according to preliminary estimates from the National Weather Service in Alabama.
In Tupelo, Mississippi, which was in the path of a tornado on Monday, police were going house to house searching for victims and trying to seal any gas leaks that could fuel fires.
More than 2,000 houses and 100 commercial properties were damaged by a tornado that ripped through the city on Monday, officials said.
Officials were also picking through the rubble in Lincoln County, Tennessee, near the Alabama state line, where a tornado touched down on Monday, killing two people.
"The roof is just wiped away from South Lincoln Elementary School," said water department worker Tammy Allen.
"They had a bus that was slammed into the front door of the school. It's all just devastating," she said.