Atlanta Fire Rescue Department spokeswoman Janet Ward said the accident happened around 10:30 a.m. and that it's not immediately clear what caused the accident.
Ward says there were 18 people on the bus at the time. A Grady Memorial Hospital spokeswoman said emergency personnel there are treating 10 people, eight with minor injuries and two serious. The other victims were taken to Atlanta Medical Center.
Ward says the bus served Hampton Inn, Fairfield Inn and Hilton hotels and was headed to Hartsfield-Jackson Atlanta International airport.
The Atlanta Journal Constitution reports that according to the markings on the bus, the shuttle was operated by MTI Limos. A call to the operations manager of the company was not immediately returned.
Overhead shots from WSB-TV show the shuttle ran into the left side of the trailer that was stretched across the road.
The shuttle bus appeared to have collided with the truck on a divided road that loops around the airport. The front of the bus was badly damaged. The windshield was cracked and it appeared to be significant damage to the engine block.
Shuttles are a common sight at the world's busiest airport, operated by hotels and off-airport parking services.