Fourteen other people were hurt in the accident in northeastern Tennessee, including eight who were in critical condition. 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.
The group of seniors, known as Young at Heart, had been to the 17th annual Fall Jubilee in Gatlinburg, Tenn., an event featuring gospel singers and speakers. Its website described the gathering as "three days of singing, laughing and preaching" for "mature and senior believers."
Inside the Statesville church, people were crying and hugging each other. One woman whispered, "It's going to be all right" while hugging another woman. A memorial service was held Wednesday evening. Police cordoned off the church to prevent reporters from talking to those who attended.
Following the service, Front Street Baptist associate pastor Rick Cruz remarked, "This is a time of difficulty, but we trust in God ... that He's fair. ... All your prayers are appreciated."
George Stadfeld, who has been a member of the church for eight years, said he knew everyone on the bus.
"We're all shaken," he said. "As bad as it is, they're all Christians and I know where they're at. I'll join them later."
Dionne Stutts, wife of Front Street Baptist senior pastor Tim Stutts, said her husband and another pastor from the church were en route to the wreck site.
"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."
Authorities said the bus crossed the median and the cable barriers that divide the interstate about 2 p.m., clipped the oncoming SUV and slammed into the tractor-trailer, which burst into flames.
Several hours after the crash, clouds of smoke still rose from the tractor-trailer and tree branches that lined the highway were charred.
The bus was on its side next to the tractor-trailer, lying across two lanes of traffic and extending partially into the median.
The bus itself didn't actually catch on fire, but there was some "heat exposure," Jefferson County Emergency Management Director Brad Phillips said. Emergency responders were able to remove people who were alive rapidly to get them away from the flames and other Good Samaritans provided assistance.
The SUV was about 50 yards away from the tractor-trailer. It was still upright, but the back half had been completely ripped off.
The interstate was completely shut down in both directions, and the scene was eerily quiet, despite the presence of many emergency workers.
"This is an extremely horrific event," Tennessee Highway Patrol spokesman Sgt. Bill Miller said at an evening news conference.
He said authorities don't know yet what caused the tire to blowout.
The injured were taken to the University of Tennessee Medical Center in Knoxville. In addition to those in critical condition, two were in serious condition and four were stable.
State Department of Safety and Homeland Security spokeswoman Dalya Qualls said in an email 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.
None of the victims were identified.
At the church, Jerry Wright said his 73-year-old brother, John, and his wife were on the bus, and he thinks his brother may have been driving the church bus because he had done so in the past.
"If he was driving, it's going to be bad," said Jerry Wright, 71. "I've been trying to ring them. I've been calling their phone, but it keeps ringing and ringing and ringing."
Brady Johnson, superintendent of the Iredell County-Statesville City Schools, said a lot of people who work for the school system are church members. Johnson said he knew people on the bus and they were awaiting word on the conditions.
Johnson said the church had adopted N.B. Mills Elementary School, providing volunteers and school supplies for needy children.
Now, the school system is offering a high school auditorium as a site for a memorial.
"It hits the community as a whole when tragedy strikes. The whole community comes together," he said.
Loller reported from Nashville. Associated Press Writer Mitch Weiss in Statesville and Skip Foreman in Charlotte, N.C., contributed to this report.