Three residents of Cincinnati in Arkansas were killed by a twister early on Friday morning.
Tornadoes were later spotted near St Louis, Missouri and were blamed for the death of three people in the southern part of the state, authorities said.
One resident of Robertson, Missouri said his neighbour's house was destroyed.
Five victims from the area were in critical condition, said Washington Regional Medical Center spokeswoman Terry Fox.
She said she had also heard reports that "several people were trapped."
Six homes and four chicken production facilities were destroyed in the storm, while five homes suffered moderate to heavy damage, said Matt Garrity, the county's manager of emergency services.
A fire station, three buildings, and one store were also damaged, he said, and an airport that serves northwestern Arkansas has closed due to debris in the area.
"We are in part of tornado alley," Garrity explained. "So even a small storm does a lot of damage."
He said emergency crews are currently surveying the extent of damage and "making sure that no one is trapped."
The Arkansas Department of Emergency Management issued a tornado advisory as bad weather lingered in the state, instructing residents to seek shelter in their home's interior rooms or on its lowest floor.
"When a tornado is sighted, the most important rule is to get low and stay low," the statement said.
A series of storms have moved through Oklahoma and into northwest Arkansas and southwest Missouri.
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