James Sykes, a survivor, described watching a "silent monster" suck up the city's streets. "It was full of lightning, devastating everything," Mr Sykes said. Dozens of businesses and emergency service buildings across the city were wiped out.
"We had a major catastrophic event here in Alabama," said Robert Bentley, the state's governor. "We have major destruction in the state." A million people were left without power.
Storms caused the Browns Ferry nuclear power plant near Huntsville, Alabama, to lose power. Officials described the incident as a low-level emergency and said it was under control.
The National Weather Service said it had received 137 tornado reports on Wednesday, bringing to 300 the total number counted in the region since Friday.
In Mississippi, at least 32 people were killed. Another 30 were reported dead in Tennessee, 11 in Arkansas, 13 in Georgia, seven in Virginia, and three in Missouri.
President Barack Obama, who promised swift assistance from the National Guard, said: "Our hearts go out to all those who have been affected by this devastation". He will travel to Alabama to view the damage on Friday.
Mr Obama also paid tribute to the "heroic efforts" of those who were responding to the disaster by clearing up disaster-struck areas and searching for victims.
People throughout the south were left trapped in their homes, colleges and vehicles after fallen trees and flooding left large areas impossible to pass.
Tim Holt, a hotel worker in Ringgold, the hardest hit town in Georgia, said: "Our town is in pieces", adding: "It's an 80 per cent loss." Birmingham, Alabama's largest city, was also struck. Samantha Nail, a resident of one of its suburbs, described watching nearby brick houses being swept away.
"We were in the bathroom holding on to each other and holding on to dear life," she said. "If it wasn't for our concrete walls, our home would be gone like the rest of them." The storms appeared to have been the deadliest natural disaster in the US since Hurricane Katrina, which killed more than 1,800 people in Louisiana in 2005.
It was also the deadliest tornado system since the "super outbreak" of April 1974, when 310 people were killed in 148 twisters across 13 states.
Further heavy rain and high winds are expected on Saturday, with 21 states throughout the country warned that they could face severe weather.