A tornado roared into southeast Alabama and killed at least 22 people and injured several others on Sunday, part of a severe storm system that caused catastrophic damage and unleashed other tornadoes around the Southeast.

'We are at 22 right now. Unfortunately, I feel like that number may rise yet again,' Lee County Sheriff Jay Jones said of the death toll.

Drones flying overheard equipped with heat-seeking devices had scanned the area for survivors but the dangerous conditions halted the search late on Sunday, Jones said. An intense ground search would resume on Monday morning.

Jones said the twister traveled straight down a key local artery in Beauregard and that the path of damage and destruction appeared at least half-a-mile wide. He said single-family homes and mobile homes were destroyed, adding some homes were reduced to slabs. He had told reporters earlier that several people were taken to hospitals, some with 'very serious injuries'.

The damaged Buck Wild Saloon, located on US Highway 280, east of Smiths Station, Alabama. AP

Lee County Coroner Bill Harris told The Associated Press that he had to call in help from the state, because there were more bodies than his four-person office can handle.

The National Weather Service confirmed late Sunday a tornado with at least an F3 rating and a track at least 8 km wide caused the deadly destruction in Alabama

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Dozens of emergency responders rushed to join search and rescue efforts in hard-hit Lee County after what forecasters said they think was a large tornado touched down Sunday afternoon, unleashed by a powerful storm system that also slashed its way across parts of Georgia, South Carolina and Florida.

Radar and video evidence showed what looked like a large tornado crossing the area near Beauregard shortly after 2 pm on Sunday, said meteorologist Meredith Wyatt with the Birmingham office of the National Weather Service.

'It appears it stayed on the ground for at least a mile and maybe longer,' Jones told the AP.

After nightfall on Sunday, the rain had stopped and pieces of metal debris and tree branches littered roadways in Beauregard. Two sheriff's vehicles blocked reporters and others from reaching the worst-hit area. Power appeared to be out in many places.

President Donald Trump tweeted late on Sunday, 'To the great people of Alabama and surrounding areas: Please be careful and safe. ... To the families and friends of the victims, and to the injured, God bless you all!'

People walk amid debris in Lee County, Alabama, on Sunday. AP

Rita Smith, spokesperson for the Lee County Emergency Management Agency, said about 150 first responders had quickly jumped in to efforts to search the debris after the storm struck in Beauregard. At least one trained canine could be seen with search crews as numerous ambulances and emergency vehicles, lights flashing, converged on the area.

No deaths had been reported on Sunday evening from storm-damaged Alabama counties outside Lee County, said Gregory Robinson, spokesperson for the Alabama Emergency Management Agency. But he said crews were still surveying damage in several counties in the southwestern part of the state.

Numerous tornado warnings were posted across parts of Alabama, Georgia, Florida and South Carolina on Sunday afternoon as the powerful storm system raced across the region. Weather officials said they confirmed other tornadoes around the region by radar alone and would send teams out early Monday to assess those and other storms.

In rural Talbotton, Georgia, about 130 km south of Atlanta, a handful of people were injured by either powerful straight-line winds or a tornado that destroyed several mobile homes and damaged other buildings, said Leigh Ann Erenheim, director of the Talbot County Emergency Management Agency.

Televised broadcast news footage showed smashed buildings with rooftops blown away, cars overturned and debris everywhere. Trees all around had been snapped bare of branches.

A vehicle is caught under downed trees along Lee Road 11 in Beauregard, Alabama. AP

'The last check I had was between six and eight injuries,' Erenheim said in a phone interview. 'From what I understand it was minor injuries, though one fellow did say his leg might be broken.'

She said searches of damaged homes and structures had turned up no serious injuries or deaths there.

Henry Wilson of the Peach County Emergency Management Agency near Macon in central Georgia said a barn had been destroyed and trees and power poles had been snapped, leaving many in the area without power.

Authorities in southwest Georgia are searching door-to-door in darkened neighborhoods after a possible tornado touched down in the rural city of Cairo, about 53 km north of Tallahassee, Florida, on Sunday evening. There were no immediate reports of serious injuries.

Authorities said a tornado was confirmed by radar in the Florida Panhandle late on Sunday afternoon. A portion of Interstate 10 on the Panhandle was blocked in one direction for a time in Walton County in the aftermath, said Don Harrigan, a meteorologist for the National Weather Service in Tallahassee.

'There's a squall line moving through the area,' Harrigan told AP. 'And when you have a mature line of storms moving into an area where low level winds are very strong, you tend to have tornadoes developing. It's a favorable environment for tornados.'

The threat of severe weather continued into the late-night hours. A tornado watch was in effect for much of eastern Georgia, including Athens, Augusta and Savannah. The tornado watch also covered a large area of South Carolina, including the cities of Charleston and Columbia.