Homes were destroyed and thousands left without power after storms caused devastation across several states.
According to the Washington Post, more than 60 tornado reports have been recorded.
States including Arkansas, Tennessee, Illinois, Indiana, Alabama and Mississippi have all had fatalities as a result of the weather.
One storm shredded through the Arkansas town of Wynne - a community some 170km east of the state capital, Little Rock.
Ashley Macmillan said she, her husband and their children huddled with their dogs in a small bathroom as a tornado passed, "praying and saying goodbye to each other, because we thought we were dead".
A falling tree seriously damaged their home, but they were unhurt.
She told the AP news agency: "We could feel the house shaking, we could hear loud noises, dishes rattling. And then it just got calm."
Governor Sarah Huckabee Sanders declared a state of emergency in the state of Arkansas on Friday, with the national guard activated to help with recovery efforts.
She said she had spoken to President Joe Biden about the situation, who promised federal aid.
As storms continue to work their way east, hundreds of thousands of people are without power across several states.
Virginia, Ohio and Pennsylvania are the worst affected, according to the US PowerOutage website.
Friday's storms also led to the collapse of a theatre roof at a packed heavy metal gig in Belvidere, Illinois state, leading to one death and 28 injuries.
The deadly tornadoes come a week after a rare, long-track twister killed 26 people in Mississippi.
Biden visited the state on Friday to pay his condolences.
In a bulletin, the Storm Prediction Center warned some of the projected tornadoes could track across the ground for long distances.
The Mississippi tornado last week travelled 94km and lasted about an hour and 10 minutes - an unusually long period of time for a storm to sustain itself. It damaged about 2000 homes, officials said.
The damaged remains of the Walnut Ridge neighborhood is seen on March 31, 2023 in Little Rock, Arkansas. Photo: BENJAMIN KRAIN