Fourteen more were injured in the crash, which involved a church bus, a tractor-trailer and an SUV.
Six of the people killed were on the bus. One each from the other vehicles was killed: the driver of the tractor-trailer and a person in the SUV, a Chevrolet Tahoe.
Dalya Qualls, public information officer in the Tennessee Department of Safety and Homeland Security, said that the bus's left front tire blew out as it was moving eastbound on I-40 in Jefferson County around 2 p.m.
The blowout threw the bus across the eastbound lanes, clipping the Tahoe on the way. It then careered across the median, striking the westbound tractor-trailer on its side.
The bus's impact immediately caused a fire in the rig, Qualls said.
Three people were riding in the Tahoe, one in the tractor-trailer, and 18 in the bus from Front Street Baptist Church in Statesville, N.C.