The Mississippi Emergency Management Agency said in a Twitter post that search and rescue teams from local and state agencies were deployed to help victims impacted by the tornadoes.
The agency confirmed early on Saturday that 23 people had died, four were missing and dozens were injured.
A few minutes later, the agency tweeted: "Unfortunately, these numbers are expected to change."
The National Weather Service confirmed a tornado caused damage about 60 miles north-east of Jackson, Mississippi.
The rural towns of Silver City and Rolling Fork reported destruction as the tornado swept northeast at 70 mph without weakening, racing towards Alabama through towns including Winona and Amory into the night.
Rolling Fork Mayor Eldridge Walker told CNN that his town was essentially wiped out.
"My city is gone. But we are resilient and we are going to come back strong," he said.
The National Weather Service issued an alert as the storm was hitting that did not mince words: "To protect your life, TAKE COVER NOW!"
"You are in a life-threatening situation," it warned. "Flying debris may be deadly to those caught without shelter. Mobile homes will be destroyed. Considerable damage to homes, businesses, and vehicles is likely and complete destruction is possible."
Cornel Knight told The Associated Press that he, his wife and their three-year-old daughter were at a relative's home in Rolling Fork when the tornado struck. He said the sky was dark but "you could see the direction from every transformer that blew".
He said it was "eerily quiet" as that happened. Mr Knight said he watched from a doorway until the tornado was, he estimated, less than a mile away. Then he told everyone in the house to take cover in a hallway.
He said the tornado struck another relative's home across a wide corn field from where he was. A wall in that home collapsed and trapped several people inside.
As Mr Knight spoke to AP by phone, he said he could see lights from emergency vehicles at the partially collapsed home.
The Sharkey-Issaquena Community Hospital on the west side of Rolling Fork was damaged, WAPT reported. The Sharkey County Sheriff's Office in Rolling Fork reported gas leaks and people trapped in piles of rubble, according to the Vicksburg News. Some law enforcement units were unaccounted for in Sharkey, according to the newspaper.
Matt Elliott, warning coordination meteorologist at the National Oceanic and Atmospheric Administration's Storm Prediction Centre in Norman, Oklahoma, said the severe weather was expected across several states.
The Storm Prediction Centre warned the greatest threat of tornadoes would come in portions of Arkansas, Louisiana, Mississippi and Tennessee.
Storms with damaging winds and hail were forecast from eastern Texas and southeastern Oklahoma into parts of southeastern Missouri and southern Illinois.
According to poweroutage.us, 46,000 customers were without power in Tennessee; 15,000 customers were left without power in Mississippi; and 20,000 were without power in Alabama.