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At least two people have been killed and others injured as tornadoes, high winds, lightning, hail and heavy rain left a trail of destruction from Texas to Alabama.
A tornado that touched down about 150 miles southwest of Little Rock in Arkansas killed a man and injured his wife when their home was destroyed.
Louisiana governor, Bobby Jindal, declared a state of emergency as thousands were left without power.
Two tornadoes also hit Missouri, toppling trees and causing some roof damage, according to the US National Weather Service.
A tree crushed a mobile home just north of Birmingham, Alabama, killing a 75-year-old woman and injuring her husband.
The extreme weather was expected to continue yesterday, with an estimated 36 million people in its path, the BBC reported.
The US Storm Prediction Centre said cities at risk included Memphis, Nashville, Houston, Indianapolis, New Orleans and St Louis.