A deadly string of tornadoes cut a swath of destruction across the US midwest, killing at least 11 people and threatening scores more as a massive storm pushed eastward early Thursday.

Homes were smashed to bits, 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 ominous 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 while most were still sleeping at around 4:30 am (1030 GMT) on Wednesday.

At least six people were killed and more than 100 injured in this southern Illinois town of 9,000.

The monster twister packed winds up to 170 miles (270 kilometers) per hour and damaged or destroyed up to 300 homes and 25 businesses, smashing a strip mall to bits and tearing a wall off the local hospital.

"A lot of the houses are unreal, it's like a war zone," fire chief Bill Summers told reporters.

Rescue crews were digging through the rubble to search for survivors, but Summers said that by late afternoon all those reported missing had been accounted for.

Harrisburg mayor Eric Gregg called the destruction and loss of life "devastating" and vowed to protect and care for those who were hurt and displaced.

"Dealing with a tornado like this is heartbreaking," he said at a press conference.

"We will build this city. We will make this city strong. This will not stop us. It will make us stronger."

Angela Capps was among those who sought shelter at the First Baptist Church.

A neighbor called her to warn her of the twister, so Capps and her children were able to take cover and escape injury.

"We haven't cried yet, for the kids," Capps said as she sat with her neighbor while their children played nearby at the Harrisburg shelter.

"I'm sure we'll go in the bathroom eventually and bawl our eyes out."

The National Weather Service has received 30 reports of tornadoes in six states since the storm began 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 Wednesday before drifting towards the eastern seaboard.

"It's a very large storm," said Corey Mead, lead forecaster for the weather service's storm prediction center Wednesday.

The governor of Illinois issued a state of emergency and went to Harrisburg to tour the damage.

"My heart goes out to the victims of this devastating storm, and I would like to thank the many people who have stepped up and volunteered to aid their neighbors," Governor Pat Quinn said.

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

"These storms have caused extensive damage across Missouri, and widespread damage and debris continue to pose significant risk to lives and property," Governor Jay Nixon said.

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.

The deadly storm marks an early start to tornado season in a region still recovering from record-breaking severe weather outbreaks.

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.

Two bad days accounted for nearly all the deaths: an outbreak of dozens of tornadoes that killed 314 people in five states on April 27 and a nearly mile-wide twister that struck Joplin, Missouri on May 22, killing 159 people.

Some 95 tornadoes struck the United States in January, causing just two fatalities, the weather service said.