Flooding in southeast Louisiana and southern Mississippi shut down roads, cutting off at least one town as an area of low pressure slowly moved west along the Gulf Coast.
Louisiana Governor John Bel Edwards declared a state of emergency, calling the flooding "unprecedented."
"We have record levels of flooding along rivers and creeks," he told reporters during a news conference, urging residents who have been advised to evacuate to leave their homes.
Emergency services were transporting residents by high-water vehicles, boats and aircraft, he said. More than 1,000 residents had been evacuated in Louisiana, the authorities said.
"We were walking out and he slipped and fell," his roommate Vernon Drummond told the station. "He went under the water. We tried to save him, but we couldn't."
The area recorded 10 to 15 inches (25.4 to 38.1 cm) of rain, David Roth, a meteorologist with the National Weather Service, told AFP. Another 10 inches were expected in parts of Louisiana over the next two days.
Layton Ricks, president of Livingston parish in the Baton Rouge area, told reporters that "we're experiencing one of the worst storm events we've ever had, with flash flooding."
Roads that had never flooded were under water, he said, adding that the backlog of people waiting to be rescued was as long as 150, even after the more than 1,000 rescue operations carried out so far.
The National Weather Service warned of "significant flash flooding" through the weekend as rains move north and west.
"A low- to mid-level cyclone over the Lower Mississippi Valley will slowly begin to lift northward into the Middle Mississippi Valley by Sunday evening into Monday," it said.
On the East Coast, meanwhile, millions of Americans residents are sweating through a heat wave amid extreme weather warnings in New York, Philadelphia, and Washington DC.
The combination of heat and humidity would make it feel as hot as 110 degrees Fahrenheit (43 degrees Celsius) in those cities.
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