Wynne's Police Chief Richard Dennis, told NBC affiliate KAIT of Jonesboro, Ark., that the city of roughly 8,000 suffered “total destruction.”
St. Francis County Coroner Miles Kimble said two people were killed in Wynne. Additional details about their deaths weren't immediately available.
Further north in Indiana, two people were confirmed dead after a tornado swept through Sullivan County, state police confirmed early Saturday.
There was no indication as to how exactly the two individuals died, Sgt. Matt Ames told NBC News, adding that the names of the deceased had not been released.
Several residences had been destroyed and trees had downed onto power lines, he said. He added that no additional injuries had been reported.
Elsewhere in Illinois, Belvidere Fire Chief Shawn Schadle said approximately 260 people were attending a heavy metal concert at the city's Apollo Theatre when the roof collapsed during a tornado.
“At the time of the collapse, we initiated a large scale response with numerous agencies,” he said, adding, “There were multiple injuries. There was a fatality.”
He said first responders also rescued someone from an elevator and had to grapple with downed power lines outside the theater in the city around 70 miles west of Chicago.
The destructive weather came as President Joe Biden toured the aftermath of a deadly tornado that struck in Mississippi one week ago and promised the government would help the area recover.
The twister that touched down in North Little Rock on Friday afternoon also damaged Jacksonville and Sherwood, meteorologist Travis Shelton said.
A spokeswoman for the emergency management agency in Pulaski County, which includes Little Rock, said 50 people had been hospitalized. Baptist Health Medical Center was treating 21 people at two facilities in the Little Rock area, with five in critical condition, a spokeswoman for the health system said.
Images from Little Rock and the surrounding area showed battered vehicles, downed power lines, toppled trees and mangled homes. A photo broadcast by NBC affiliate KARK of Little Rock showed a Baskin Robbins where the side of the building appeared to have been sheared off.
Kenneth Bruton was leaving a grocery store when he got in his pickup, looked back and saw the tornado coming over a hill.
“I got out of my truck and started running for shelter,” Bruton told KARK. The force of the wind knocked him down on his face, he said, but he was able to make it into a salon.
“And as I got in, huddled up against the cement barrier, every single glass window blew out, and people were blown back,” Bruton said. “And I held on. And it must have been a minute just huddled. I thought I was a goner for sure.”
The Arkansas State Emergency Operations Center issued a full activation in response to the severe weather Friday afternoon, according to a statement.
By early Saturday, over 192,000 customers were without power in Illinois, Indiana, and Arkansas, according to poweroutage.us.
Flash flooding from thunderstorms also posed a risk from Midwest to the Lower Mississippi Valley on Friday, according to the National Weather Service. The areas with the greatest risk for flooding through Friday night are across the Ohio, Tennessee, and Lower Mississippi valleys.