Local news showed roofs torn off homes and large trucks overturned.
Eight people died in Kansas in a crash involving more than 50 vehicles, caused by low visibility during a "severe dust storm," local police said.
Missouri State Highway Patrol confirmed 12 storm-related fatalities and shared images of boats piled on top of one another at a marina destroyed by the weather.
The state police reported downed trees and power lines, as well as damage to buildings, with some areas severely impacted by "tornadoes, thunderstorms and large hail."
"It was the scariest thing I've ever been through, it was so fast, our ears were all about to burst," Alicia Wilson, who was evacuated from her home in Missouri, told TV station KSDK.
Further south in Mississippi, the state's governor said six deaths were reported and that three people were missing late Saturday.
Meanwhile in Texas, local authorities told AFP that four people had died in vehicle accidents linked to dust storms and fires that reduced visibility on the roads.
In the neighboring state of Arkansas, officials said three people had died and 29 had been injured in the storm.
Governor Sarah Huckabee Sanders declared a state of emergency in response and said she had spoken with President Donald Trump.
"He said to tell the people of Arkansas he loves them and he and his administration are here to help with whatever we need following last night's tornadoes," Sanders wrote on social media platform X.
The National Weather Service (NWS) warned of "severe thunderstorms" from the Lower Great Lakes to the Southeast on Sunday.
"The hazards associated with these thunderstorms are frequent lightning, severe thunderstorm wind gusts, hail, and a few tornadoes," it said in its latest forecast bulletin.
- More tornadoes forecast -
At least 250,000 homes and businesses across the central United States were without power by early Sunday morning, according to tracking site poweroutage.us.
More tornadoes were forecast in the central Gulf Coast states including Mississippi and Tennessee.
"Numerous significant tornadoes, some of which may be long-track and potentially violent, should continue into this evening," the NWS said on Saturday.
Tornadoes are spinning columns of air that touch the ground from massive cumulonimbus thunderstorm clouds.
The central and southern states of Texas, Oklahoma and Kansas get the most violent ones due to unique geographical and meteorological conditions.
Dubbed "Tornado Alley," this is where winds of widely varying temperatures meet in volatile, potent storm clouds, with most storms occurring from May to June.
In 2024, 54 people died in tornado-related incidents in the United States, according to the National Oceanic and Atmospheric Administration.
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