Fourteen other people were hurt in the crash in northeastern Tennessee, and all but two of them had been taken to hospitals, state Department of Safety and Homeland Security spokeswoman Dalya Qualls said in an email. The extent of their injuries was not immediately available.
The bus was carrying members of the Front Street Baptist Church in Statesville, N.C., which is about 140 miles east of the crash site.
Dionne Stutts, wife of Front Street Baptist senior pastor Tim Stutts, said the bus was carrying a senior adult group who was on the way home from a trip to Gatlinburg.
She said her husband and another pastor from the church were en route to the wreck.
"They had been there and they were on their way home today," she said. "We are devastated and just ask for the people to be praying."
Susan Wyatt, a spokeswoman for the University of Tennessee Medical Center, said all of the injured were adults. Four were flown to the emergency room.
Qualls said 18 people were on the bus and six of them were killed. One person among the three in the SUV was killed and the tractor-trailer driver also died.
The bus crossed the median in Jefferson County about 2 p.m. It clipped the oncoming SUV and slammed into the tractor-trailer, which burst into flames. The bus, which was heading east, overturned.
The accident shut down Interstate 40 in Jefferson County.