Six people were reportedly killed and it is feared that several hundred people may have been injured in the fast-moving storms. While a number of people are said to be trapped inside buildings.
Forecasters say up to 53 million people could be affected. Hailstones the size of tennis balls have been reported.
The rapid-moving storm - with winds of up to 111km/h (68mph) - is continuing its way east.
November is ordinarily one of the quietest months in the tornado calendar, meaning these storms are unusually destructive for this time of year, the BBC's Nick Bryant in New York reports.
'War zone'
All the fatalities were reported in Illinois, which was the hardest hit state.
One person died in the town of Washington, Melanie Arnold of the Illinois Emergency Management Agency was quoted as saying by the Associated Press news agency. She provided no further details.
Two further people died in southern Massac County, while an elderly man and his sister were killed when a tornado struck their farm house in the village of New Minden.
Eyewitnesses described how large parts of Washington had been levelled by the tornadoes.
Illinois officials are describing the situation as "dangerous and volatile".
Karen Harris, a food truck operator in Washington, told the BBC she saw a "car completely mangled, the houses gone".
"Telephone wires [are] down everywhere, live wires are still down. I'm pretty traumatised from what I saw.
"I actually saw a vehicle in the middle of the road, their left signal light turned on, like they were getting ready to turn, all the windows were out of it, blood was in the back seat.
"Pandemonium. It looks like a war zone," Ms Harris added.
Laura Nightengale, a reporter with the Journal Star newspaper in Peoria, Illinois, witnessed the approach of a tornado from inside a house in the town.
"From the window I saw this huge tornado, tonnes of debris flying through the air.
"I took shelter in the basement. The area that was hit, it's just absolutely devastated - entire blocks where homes stood this morning right now are just rubble," Ms Nightengale told the BBC.
The National Weather Service warned of a "particularly dangerous situation" for parts of the central US.
"Several rapidly moving, intense tornadoes, severe thunderstorms, large hail events and damaging winds are expected in these watch areas," the service said.
Illinois Governor Pat Quinn warned residents to "pay attention to all weather alerts and stay home and inside if possible".
American football fans were evacuated from a stadium in the centre of Chicago as one tornado moved through the city suburbs.
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