President Joe Biden called the wave of twisters, including one that traveled more than 200 miles (320 kilometers), "one of the largest" storm outbreaks in American history.
"It's a tragedy," a shaken Biden, who pledged support for the affected states, said in televised comments. "And we still don't know how many lives are lost and the full extent of the damage."
With the death toll all but certain to rise, scores of search and rescue officers were helping stunned citizens across the US heartland sift through the rubble of their homes and businesses overnight.
More than 80 people are dead in Kentucky alone, many of them workers at a candle factory in Mayfield, the state's Governor Andy Beshear said Sunday as he raised the confirmed toll by 10 fatalities.
And the forecast was grim. "That number is going to exceed more than 100," Beshear told CNN.
Meanwhile, at least six died in an Amazon warehouse in Illinois where they were on the night shift processing orders ahead of Christmas.
Emergency crews worked through the night into Sunday at both locations, but the Kentucky governor's somber remarks suggested his state's residents should brace for the worst.
Of the 110 employees working Friday night in the candle factory, "about 40 of them have been rescued and I'm not sure we're going to see another rescue," Beshear said.
"I pray for it," he said, but "it would be an incredible miracle" if more factory victims were found alive.
As Americans grappled with the immensity of the disaster, condolences poured in, with Pope Francis saying he is praying "for the victims of the tornado that hit Kentucky."
Biden's Russian counterpart Vladimir Putin, in a break from tense bilateral relations, said his country "shares in the grief" of those who lost loved ones and expressed hope that victims quickly overcome the tornadoes' consequences.
The catastrophe has shaken many Americans, including officials who have worked in the aftermath of tornadoes and other big storms.
"This event is the worst, most devastating, most deadly tornado event in Kentucky's history," Beshear said Saturday, adding he fears "we will have lost more than 100 people."
"The devastation is unlike anything I have seen in my life, and I have trouble putting it into words."
The head of the US Federal Emergency Management Agency, Deanne Criswell, was to arrive in Kentucky Sunday.
The largest tornado among the swarm that smashed through the US South and Midwest had rumbled along the ground for over 200 miles (320 kilometers), Beshear said, one of the longest on record.
The longest a US tornado has ever tracked along the ground was a 219-mile storm in Missouri in 1925. It claimed 695 lives.
'Hope For A Miracle'
The western Kentucky town of Mayfield was reduced to "matchsticks," its mayor Kathy O'Nan said.
"There's always hope" for survivors among the missing, O'Nan told NBC Sunday. "We hope for a miracle in the days to come."
The town of 10,000 was described as "ground zero" by officials, and appeared post-apocalyptic: city blocks leveled; historic homes and buildings beaten down to their slabs; tree trunks stripped of their branches; cars overturned in fields.
Some Christmas decorations could still be seen by the side of the road.
David Norseworthy, a 69-year-old builder in Mayfield, said the storm blew off his roof and front porch while the family hid in a shelter.
"We never had anything like that here," he told AFP.
In one demonstration of the storms' power, when winds derailed a 27-car train near Earlington, Kentucky, one car was blown 75 yards up a hill and another landed on a house. No one was hurt.
Deaths In Multiple States
Reports put the total number of tornadoes across the region at around 30.
At least 14 people were killed in other storm-hit states, including six at the Amazon facility in Illinois.
Four were killed in Tennessee, two died in Arkansas, while Missouri recorded two fatalities. Tornadoes also touched down in Mississippi.
Biden said he planned to travel to the affected areas.
Amazon Workers Trapped
At the Amazon warehouse in the southern Illinois city of Edwardsville, around 100 workers are believed to have been trapped inside.
"We identified 45 personnel who made it out of the building safely... and six fatalities," Edwardsville fire chief James Whiteford told reporters.
But he said the operation had turned from rescue to focus "only on recovery," fueling fears the toll will rise.
Amazon chief Jeff Bezos said he was "heartbroken" at the deaths.