Four people were killed as tornadoes moved through northern Mississippi, officials said, and two in Tennessee and one in Arkansas.
There have been reports of at least 20 tornadoes of varying severity.
The high winds have also caused significant damage to homes.
Authorities in parts of Mississippi - where a seven-year-old was among those killed - are conducting a house-by-house search-and-rescue operation after the state was hit by multiple tornadoes.
The boy was inside a car, which was picked up and tossed in the storm. His relatives, who were also in the car, were taken to a hospital for treatment.
Planes at a small airport in the north-west of the state were overturned and an unknown number of people were injured.
"I'm looking at some horrific damage right now," Clarksdale Mayor Bill Luckett was quoted by the AP news agency as saying.
"Sheet metal is wrapped around trees; there are overturned airplanes; a building is just destroyed."
Mississippi's Interstate 55 was closed in both directions as the tornado approached, the state's Highway Patrol said.
The bad weather is also due to hit - or has hit - the states of Kentucky, Alabama, Indiana, Illinois, Missouri and Alabama.
The national Storm Prediction Center in Oklahoma released a "particularly dangerous situation" warning for the first time since June 2014 when two massive tornadoes destroyed a rural Nebraska town, killing two people.
The possibility of bad weather just before Christmas in the US is not unusual, officials at the centre say.
One year ago a tornado hit south-eastern Mississippi, killing five people and injuring dozens more.
A storm on Christmas Day in 2012 which included several tornadoes damaged  homes from Texas to Alabama.
A storm described by forecasters as "particularly dangerous" has hit the South and Mid-west of the US, killing at least seven people and injuring scores more ahead of Christmas.