The Piper PA-32 apparently ran into trouble not long afterword taking off, Federal Aviation Administration spokesman Kathleen Bergen said.
Witnesses said the blaze prevented anyone on the ground from helping any victims in the wreckage. Those who tried included commercial truck driver Gerald Smith.
Smith said that as the aircraft plummeted, he had just enough time to slam on his brakes. He saw the plane swooping in low toward the passenger door of his tractor-trailer.
The tail, other wreckage and charred concrete could be seen at the median barrier where the plane crashed. Smaller debris littered the area, including a propeller lying on the roadway about 40 feet (12 meters) from most of the wreckage.
Emergency officials shut down Interstate 285 in both directions, causing large traffic jams. The Georgia Department of Transportation said some lanes near the crash site could be closed for eight hours.