A deadly string of tornadoes cut a swath of destruction across the US midwest, killing at least 11 people.

Homes were destroyed, cars were tossed into lakes, trees were uprooted and shops were reduced to rubble in towns from Nebraska to Kentucky as the powerful system whipped up strong winds, hail and funnel clouds.

The town of Harrisburg, Illinois was the hardest hit after it was ripped apart by a deadly twister that stayed on the ground for miles, striking at around 4.30am yesterday.

At least six people were killed and more than 100 injured.

The twister packed winds up to 270kph and damaged or destroyed up to 300 homes and 25 businesses, smashing a strip mall and tearing a wall off the local hospital.

The National Weather Service received 30 reports of tornadoes in six states since the storm began on Tuesday, battering Nebraska and Kansas before rolling eastward to Missouri, Illinois, Indiana and Kentucky.

Severe thunderstorms pounded Alabama, Georgia, Kentucky, Mississippi, North Carolina and Tennessee before drifting towards the eastern seaboard.

Missouri's governor called in the national guard to help with the clean-up after at least three people were killed by tornadoes which ripped across the southern portion of the state.

Another two people were killed when the storm moved over eastern Tennessee, and a third person was feared dead, but authorities have not yet been able to search the rubble for the body, a state emergency management official said.

Some 545 people were killed by tornadoes in 2011, which was the deadliest tornado season since 1936 and the third worst on record, according to the national weather service.