"We have now five confirmed dead -- four under 18, one adult driver. We initially said six dead, but that person is in critical condition at last word," said Texas Department of Public Safety spokesman Tom Vigner.
"We do not know the cause of the wreck at this time," Vigner said.
Police said helicopters flew about 15 people to area trauma centers and another 20 were rushed to hospitals by ambulance.
About 50 people were on board the bus when it crashed in the city of Terrell. The bus had completed about 30 miles of a 240-mile trip to a religious camp in Ruston, Louisiana, he said.
"There were bodies and blood and things everywhere," said Todd Von Helms, a youth minister in another church group that was traveling on the highway to the same camp. "I asked our youths to turn their heads and not to look. It's probably the worst thing I've ever witnessed."
Public safety officials said they did not have any immediate information on the 15 people flown from the scene of the crash.
Investigators noted there were no skid marks on the highway, which indicated the bus did not slow down before hitting a concrete pillar on the embankment. The front of the bus was severed by the impact and a large section of its flank was peeled off by the pillar.
The bus was carrying students from the Metro Church of Garland, a suburb east of Dallas, to a youth church retreat in Louisiana when it struck the embankment under a bridge on an interstate highway, east of Dallas.
David Eden, a pastor at the Garland church said the passengers were school students heading to a week-long church retreat.
He said several of the students called him from the scene by cell phone.
"They said the bus tipped over and hit the pole, and everyone was freaking out and screaming," Eden told reporters.
Sean Burns, a deacon at the church told a press conference that about 100 students from the church were headed to the summer retreat on two buses. Church officials went to various hospitals to console the victims and their families.
"This is a horrible accident and there is a lot of chaos," Burns said. "The church family is turned upside down."
It was the latest in a number of multiple-fatality accidents this year on Interstate 20, a major east-west artery across Texas.
On June 10, a 35-year-old woman and four children were killed when their sport utility vehicle smashed into an 18-wheeler parked on the shoulder in Mesquite, a Dallas suburb.
The day before, three people were killed when a bus slammed into the rear of tractor-trailer near Colorado City in West Texas.
In late March, five students from Nigeria were killed when their sport utility vehicle veered off the interstate west of Fort Worth.