Rescue workers at the scene were pulling the dead and injured from the wreckage of homes and businesses in the worst affected areas in Lee County, which includes the state's largest city of Auburn.
County Sheriff Jay Jones said the "tornadoes outbreak" had caused "catastrophic" damage and there were fears more bodies would be found.
"The challenge is the sheer volume of the debris where all the homes were located. It's the most I've seen that I can recall," he told CNN.
The death toll stood at 23 in the early hours of Monday with authorities warned that it is expected to rise.
Tornado warnings were in force across Georgia and Alabama on Sunday evening.
The most devastating tornado struck the area around Beauregard in Lee County at around 2pm on Sunday, the National Weather Service (NWS) said.
The NWS classified it as at least an F3 rating, meaning winds of up to 165mph. and said it carved a path at least half a mile wide.
After the tornado hit, drones flying overhead equipped with heat-seeking devices scanned the area for survivors. But the dangerous conditions halted the search late on Sunday.
Kay Ivey, Alabama's governor, warned residents on Twitter that more severe weather might be on the way.
She said the state was working to help families who had been impacted.
The East Alabama Medical Centre in Opelika said in a statement that it was treating more than 40 patients as a result of the tornado and expected to receive more. Some patients have been sent to other hospitals, it added.
The storm also left more than 10,000 customers without power, the Birmingham News said, citing the utility Alabama Power.
After the tornado hit Alabama on Sunday afternoon, it unleashed by a powerful storm system that also slashed its way across parts of Georgia, South Carolina and Florida.
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.
Authorities in southwest Georgia are searching door-to-door in darkened neighbourhoods after a possible tornado touched down in the rural city of Cairo on Sunday evening. There were no immediate reports of serious injuries.
A tornado was also confirmed by radar in the Florida Panhandle on Sunday afternoon, authorities said.
In response to the destruction in Alabama, Donald Trump tweeted late on Sunday night urging resident to take care.
To the great people of Alabama and surrounding areas: Please be careful and safe. Tornadoes and storms were truly violent and more could be coming,” he wrote.
“To the families and friends of the victims, and to the injured, God bless you all!
A tornado watch remained in place on Sunday evening 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.
Additional reporting by AP and Reuters
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