More than 100 deaths across a half-dozen states have been attributed to the powerful storm that slammed into Florida's Big Bend region late on Thursday before cutting a destructive path through Georgia and into the Carolinas.
States affected are North Carolina, South Carolina, Georgia, Florida, Tennessee and Virginia.
As many as 600 people remain missing, US Homeland Security adviser Liz Sherwood-Randall said at the White House, though she noted that the numbers could vary as responders reach more locations.
The death toll was likely to rise, officials said.
Millions are without power and roads and bridges have been destroyed due to dramatic flooding.
With cellphone towers down across the region, hundreds of people had yet to make contact with loved ones and were listed as unaccounted for.
In mountainous Buncombe County, which includes the popular tourist destination of Asheville, 35 people have died, the county sheriff said at a news briefing on Monday.
The county was set to begin distributing food and water to residents later in the day. Some supplies had to be airlifted to the region with most major routes blocked by mudslides and flooding.
"They're running out of gas for ATVs that are helping the rescue, they're also running out of gas for the chainsaws," said Colleen Burns, 58, whose house is near Burnsville, in neighbouring Yancey County. "We desperately need gas."
Elsewhere in Yancey, the storm snapped century-old trees around the home of Taylor Shelton, 44. It took her husband two days with a chainsaw to cut a passage through the felled trees in their driveway and the nearby road so they could drive themselves and their three children out of the darkened house.
With no phone service, they relied on a neighbour who works as an EMT and had a walkie-talkie to help them determine which back roads out of the mountains were passable.
"The devastation is unbelievable," she said in a phone interview.
They were attempting to drive back home on Monday to pick up their dog and two guinea pigs and leave out food for the cat and the chickens. Their car was loaded with coffee, donuts and diapers for their neighbours.
"It looks like War of the Worlds. Very, very big trees are down everywhere," she said. "We saw houses that are just washed away."
She has still not been able to reach her husband's parents, who live in the nearby town of Burnsville, which was also badly hit.
Lake Lure, some 32km southeast of Asheville, was covered with floating debris from homes and businesses washed away by mountain streams that surround the lake, a video posted on X by Charlotte City Councilman Tariq Bokhari showed.
"It's hard to describe - never seen anything like this, post-apocalyptic," he wrote. "It's so overwhelming. You don't even know how to fathom what recovery looks like, let alone where to start."
Some 2.1 million homes and businesses were without power on Monday, according to the website Poweroutage.us.
"The lack of communication is concerning," North Carolina Governor Roy Cooper said on Monday in an interview with CNN. "We know that there are people missing, and we know that there's going to be significant fatalities at the end of this and our prayers and our hearts go out to these families."
Cooper, who said he had not heard from his son and daughter in 72 hours, added that local officials and rescue workers were performing door-to-door welfare checks in many communities.
In Buncombe, officials said they are conducting checks of 150 "priority" households that include elderly residents or residents with medical problems.
The National Guard and emergency workers from 19 states have been deployed to help, along with Federal Emergency Management Agency personnel. Cooper said the rugged terrain in the mountains of western North Carolina makes it almost impossible to traverse with landslides and flooding.
"So we're depending a lot on air power, helicopters with hoist capacity to get supplies in," he said.
President Joe Biden said he would visit North Carolina later this week and may ask Congress to return to Washington for a special session to pass supplemental aid funding.
"There's nothing like wondering, 'Is my husband, wife, son, daughter, mother, father alive?'" Biden said at the White House. "Many more will remain without electricity, water, food and communications, and whose homes and businesses are washed away in an instant. I want them to know we're not leaving until the job is done."
Vice President and Democratic presidential candidate Kamala Harris cut short a campaign trip in Nevada on Monday to take part in briefings in Washington on the hurricane response and will visit the region when doing so won't impede response efforts, a White House official said.
Republican presidential candidate Donald Trump travelled to Valdosta, Georgia, on Monday to visit a furniture store that was heavily damaged in the storm.
Helene struck Florida's Gulf Coast on Thursday night as a major Category 4 hurricane, triggering days of driving rain throughout the South and destroying homes that had stood for decades.
Georgia Governor Brian Kemp said on Monday that at least 25 people in his state had died, including a firefighter responding to emergency calls during the storm and a mother and her 1-month-old twins who were killed by a falling tree.
Damage estimates ranged from $US15 billion to more than $US100 billion ($US23 billion to $NZ157 billion), insurers and forecasters said over the weekend.
