The driver of the tractor-trailer rig and his 9-year-old daughter were critically injured and flown by helicopter to a hospital in Nashville, about 40 miles to the north.
Two others in a pickup truck also struck by the 18-wheeler were taken to a local hospital, but a hospital official said only one was treated for injuries.
The accident was witnessed by the parents of at least two of the children who died, said Jackie Gibbs, director of Maury Regional Emergency Medical Services.
"They were just completely traumatized. They didn't have any physical injuries," said Gibbs, a paramedic who was on the scene shortly after the accident.
Authorities believe the truck was traveling southbound near the Lewisburg exit, came upon slower-moving traffic, moved into the left lane and struck a car, knocking them both into the median, said Dana Keeton, spokeswoman for the state Department of Safety. No one in the car was injured.
The rig then crossed the median and struck a Ford Ranger pickup truck, which spun off the interstate, Keeton said.
The tractor-trailer clipped the back of a dump truck being hauled on a wrecker, went back into the median and struck the car, slamming both into the rock wall, she said.
"Both the car and the truck were completely consumed by fire," Keeton said.
Keeton said the driver of the tractor-trailer rig was identified as Edward L. Farrow, 41, of Adena, Ohio. His daughter, Letisha Kay Farrow, was the injured passenger in the rig.
The impact knocked the cab free from the trailer and the rig's driver pulled his daughter out, Gibbs said.
"All he knew was he was trying to get his little girl out of the 18-wheeler and it was on fire," Gibbs said.
He said the father and daughter were the only people in the tractor-trailer and he did not know why the young girl was with her father.
Both were in critical condition at Vanderbilt University Medical Center in Nashville, suffering from burns and breathing problems, said hospital spokeswoman Leigh McMillan.
Sonja Curry, 34, of Council Bluffs, Iowa, was treated and released at Maury Regional Hospital, said Darlene Baxter, an assistant administrator at the hospital. She said another person came to the hospital with Curry, but apparently was not injured.
Identities of the other victims were not immediately known and authorities did not know where they came from or where they were going.
The northbound lanes of Interstate 65 were closed for at least four hours while troopers tried to clear the wreckage and reconstruct the accident.
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