A number of tornadoes ripped up small towns in their path late on Sunday, while huge chunks of hail the size of grapefruits destroyed houses, downed power lines and felled trees.
Two counties in Tennessee bore the brunt of the thunderstorms which carried the tornadoes, with a reported 23 deaths in the state, including an infant and a family of four.
Most of the deaths were along a 40km path stretching from Newbern, about 130km northeast of Memphis, to Bradford, officials said.
Three people died in Missouri and one in Illinois, and dozens were injured in Arkansas.
Heavy storms also battered Kentucky and Indiana.
Authorities in some localities said many people remained trapped in their homes.
"Right now we're trying to make sure there are no people left in the rubble," Tennessee Governor Phil Bredesen told CNN television.
"This morning, I made an initial disaster declaration request to President Bush for Dyer and Gibson counties where combined, an estimated 23 people lost their lives and more than 58 suffered injuries," Mr Bredesen said in a statement.
"The thoughts and prayers of our state are with those families who lost loved ones or suffered injury as a result of last night's storms. We can replace material objects, but the human costs are what cut the deepest," he said.
Rescue teams with sniffer dogs have been sent to the worst-affected area to search for anyone who may be trapped in the rubble, and National Guardsmen are helping to remove debris.
The weather service's Storm Prediction Centre in Norman, Oklahoma, said it had preliminary reports of 63 tornadoes.
Tennessee officials estimated 1,200 buildings were damaged in one county alone.
"There's just nothing left of houses but foundation," Sheriff Jeffrey Holt in Dyer County told CNN.
He said that all around him was "absolute total destruction of homes", and that widespread power outages are expected to last several days.
Mr Holt said there had been "plenty of warnings" as the storms advanced.
"The amount of destruction in the area is what caused our fatality count to get so high," he said.