The Mount Zion Baptist Church bus from Huntsville, Alabama, was on its way to the airport for a student ministry mission trip to Africa when it collided with another vehicle on a four-lane road.
Fulton County Police Corporal Partrena Smith said that at least ten people were hurt, including two critically, while Fulton County Fire Chief Larry Few said 21 were hurt.
Officials said 38 people were aboard the bus and the crash involved at least two other drivers. Authorities have not released full details about the victims or what prompted the crash.
Church education minister Terry Slay told said the bus was carrying 11th and 12th-graders, along with adults.
Images from the scene showed the bus overturned on its roof and a car underneath it.
Madison County Commissioner Phil Vandiver's wife and son were on the bus. He told reporters outside the church: "We know they're all right, we know we've been blessed."
Church members have asked for people to pray for the families involved.
Lance Roberson's neice was on the bus and he told Fox news: "We know their intentions were good, their intentions were to go out fly to Africa and do God's will but we just have to wait and see what happens."
Cpl Smith said the National Transportation Safety Board is handling the investigation.