The town of Harrisburg, Illinois 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 (10:30 GMT.)
"We've got homes toppled, cars thrown in lakes. You can't imagine how devastating it is until you're there," Harrisburg mayor Eric Gregg told CNN.
"In small communities it's just heart breaking -- we all know each other, we all care very much about each other."
Rescue crews were digging through the rubble to search for survivors and Gregg said he hoped the toll in his town of 9,000 people did not rise above the six bodies already recovered.
At least 100 people were injured by the twister that damaged or destroyed up to 300 homes and 25 businesses.
The twister also ripped a wall off the local hospital, but staff luckily received a warning in time to get all the patients away from the windows and into the central corridor so nobody was hurt.
"We're basically out there pulling -- going, you know, piece by piece, pulling material off of the top of each other to try to make sure we're not missing anyone," Gregg said.
"We're very hopeful that we can find more survivors."
The National Weather Service has received 17 reports of tornados in six states since the storm began Tuesday, battering Nebraska and Kansas, then moving eastward to Missouri, Illinois, Indiana and Kentucky.
Severe thunderstorms were expected to continue to pound Alabama, Georgia, Kentucky, Mississippi, North Carolina and Tennessee Wednesday before moving to the eastern seaboard.
"It's a very large storm," said Corey Mead, lead forecaster for the weather service's storm prediction center.
"There have been a number of tornado reports in addition to damaging winds and hail. We're expecting that threat to continue into today and tonight."
The governor of Illinois activated the state's emergency operations system and was headed to Harrisburg to tour the damage.
"Our hearts go out to their families and the many others who were injured or suffered a devastating loss," Governor Pat Quinn said.
"The state of Illinois is committed to doing everything possible to help these communities respond and recover from this disaster."
Missouri's governor also declared a state of emergency after at least three people were killed by tornadoes which ripped across the southern portion of the state, causing extensive damage in the towns of Branson, Buffalo, Cassville, Lebanon and Oak Ridge.
"As we did throughout 2011's numerous emergencies, the state of Missouri will assist at every stage of this response to keep Missouri families safe and help communities recover and rebuild," Governor Jay Nixon said in a statement.
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 tornados struck the US in January, causing just two fatalities, the weather service said.
One person was critically injured in Waubunsee, Kansas on Tuesday, the weather service said, updating an earlier report of a fatality there.
