Trapped homeowners swam to safety and others were rescued by boat as record flash flooding killed at least 16 people in eastern Kentucky and swamped entire towns, prompting a frenzied search for survivors through some of the poorest communities in America.
Heavy rain continued to pound the region on Friday and authorities warned the death toll was likely to grow sharply.
Some waterways were not expected to crest until Saturday.
It is the latest in a string of catastrophic deluges that have hammered parts of the US this summer, including St Louis earlier this week and again on Friday.
Scientists warn that climate change is making weather disasters more common.
Water poured down hillsides and into Appalachian valleys and hollows, where it swelled creeks and streams that course through small towns.
The torrent engulfed homes and businesses, trashed vehicles and crunched debris against bridges. Mudslides marooned some people on steep slopes.
Rescue teams backed by the National Guard used helicopters and boats to search for the missing but some areas were still inaccessible.
Kentucky governor Andy Beshear said the death toll was “going to get a lot higher”.
Rachel Patton said floodwaters filled her home so quickly that her mother, who is on oxygen, had to be evacuated on a door that was floated across the high water. Her voice faltered as she described their harrowing escape.
“We had to swim out and it was cold. It was over my head so it was, it was scary,” she told WCHS TV.
Mr Beshear told The Associated Press that children were among the victims, and that the death toll could more than double as rescue teams searched stricken areas.
“There are hundreds of families that have lost everything,” Mr Beshear said. “And many of these families didn’t have much to begin with. And so it hurts even more. But we’re going to be there for them.”
At least 33,000 utility customers were without power and the flooding extended into western Virginia and southern West Virginia, across a region where poverty is endemic.
The deluge in Appalachia came two days after record rains around St Louis dropped more than 12 inches in some areas and killed at least two people.
Last month, heavy rain falling on mountain snow in Yellowstone National Park triggered historic flooding and the evacuation of more than 10,000 people and ravaged areas of Montana.
In both instances, the amount of rain and flooding far exceeded what forecasters predicted.
Emergency crews in Kentucky made close to 50 air rescues and hundreds of water rescues on Thursday, and more people still needed help, Mr Beshear said.
More than 290 people have sought shelter, Mr Beshear said.
He deployed National Guard soldiers to the hardest-hit areas.
President Joe Biden called to express his support for what will be a lengthy recovery effort, Mr Beshear said, predicting it will take more than a year to fully rebuild.
The National Weather Service said another storm front adding misery to flood victims in St Louis on Friday could bring more thunderstorms to the Appalachians, where flash flooding remained possible across the region.