The powerful storms raked through the adjoining states of Kentucky, Indiana and Ohio.
"We have three known fatalities," Sheriff Randall Dodds, of Logan County in west-central Ohio, told a CBS affiliate.
"The devastation was such that we have to get heavy equipment into these areas to be able to move this material where homes have collapsed, to see if there's anybody injured," he said, adding, "it's going to take a long time."
In all, more than 13 million people in the central United States were placed under tornado watches Thursday as the storms approached, the National Weather Service (NWS) said.
Storms hopscotched across the Ohio Valley, spawning apparent tornadoes in a number of areas, including a "very dangerous half-mile-wide tornado" in Ohio, NWS said.
One tornado struck the rural town of Indian Lake in the western part of the state.
"It's pure devastation. I have never seen anything like this in my entire life," Amber Fagan, president of the Indian Lake Chamber of Commerce, told a Columbus ABC television station.
"Downtown, it's bad. It's very bad."
Downed trees, shattered glass and fallen power lines littered roads.
Further east, close to 5,000 homes were without power in Ohio's Delaware County.
"Someone else's roof is in my kitchen," Katie Sprinkle told the Columbus Dispatch newspaper. She said her children wore bike helmets during the storm and her husband had them shelter under an overturned canoe.
"Pray loud, Mom," her nine-year-old daughter urged her.
Indiana State Police initially told US media that three people died in a mobile home park in Winchester, Indiana, when a suspected tornado struck.
But at a press conference overnight they said they were "not aware" of any fatalities.
Authorities said Friday, however, that at least 38 people had suffered injuries in Indiana's Randolph and Delaware counties, including "three that are possibly critical." They said at least 22 buildings were believed to be destroyed.
In Kentucky, Governor Andy Beshear said on social media that a tornado moved through the cities of Gallatin and Trimble in his state but left no fatalities.
Tornadoes, weather phenomena that are as impressive as they are difficult to predict, are relatively common in the United States, especially in the central and southern parts of the country.
Tornado outbreaks are not uncommon in March, but their peak generally arrives in April or May.
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