At least 15 people have been killed in the states of Mississippi, Tennessee and Arkansas since Thursday, officials said.
With more severe weather expected across the central United States, forecasters are warning of airport delays and flooded roads as travelers return home after the Christmas holiday.
Feeding on unseasonably warm air, storms left a trail of destruction in rural communities from Alabama to Illinois.
More than a dozen tornadoes were reported on Friday in six southern states.
In Alabama, where Governor Robert Bentley had declared a state of emergency to deal with the heavy flooding, tornadoes uprooted trees and tore off rooftops, with one touching down in Birmingham, the state's most populous city.
"The damage was ... confined to approximately one square mile," Birmingham Fire Department Chief Charles Gordon told CNN. "We have three houses that collapsed."
No one died, but Gordon said victims were rescued from the debris.
Mississippi Governor Phil Bryant and Georgia Governor Nathan Deal also declared states of emergency in counties affected by the weather.
Forecasters at the National Weather Service warned that the central United States "will continue to have widespread showers and thunderstorms this weekend."
This weather system "has a history of producing heavy rain and flooding/flash flooding over much of the southeastern US, and the threat for excessive rainfall will persist."
The NWS warned that "flash flooding will be possible" on Saturday in the area.
In Mississippi, eight people were confirmed dead and another 60 injured, the state emergency management agency said on Twitter. Among them was a seven-year-old boy killed when a storm picked up and tossed the car he was travelling in, fire chief Kenny Holbrook told reporters in the town of Holly Springs.
Six fatalities were confirmed in Tennessee, including three people found dead Thursday in a car submerged in a creek, according to the fire department in Columbia, Tennessee.
Another person was killed in Arkansas.
The East Coast meanwhile was enjoying unseasonably warm weather, with temperatures in New York peaking at 72 degrees Fahrenheit (22 Celsius) Thursday, the warmest Christmas Eve since records began in 1871. The temperature reached a record-setting 66 degrees (19 Celsius) the following day.
In the US capital, the temperature on Friday reached 69 degrees (20.6 Celsius), a 30-year record, local media reported.
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