Rescuers were prevented from reaching victims in the wreckage of the Piper PA-32 craft due to an intense blaze on the ground.
Captain Eric Jackson, of the DeKalb County Fire Department, said it was a "miracle" no other vehicles had been hit.
"It's a miracle, literally a miracle, that no other cars were hit," he told reporters.
Jackson confirmed that all four people on board the plane died in the crash. Their identities have not yet been released.
'Like a bomb being dropped'
"You could see him trying to get the nose of the plane up," witness Don McGee told WSB-TV. "It was edging up, and then it just dropped."
"The impact was large, like a bomb being dropped," he said.
Another witness, Gerald Smith, told WSB he was almost hit by the plane as he drove his tractor trailer.
"It was flying very low. It wasn't higher than the top of my truck," he said. "I guess it was just God telling me to slam on my brakes.. by the time I did hit the brakes, I heard an impact hit the front of my truck. I looked back to my left once I stopped the truck and that plane was up against the wall burning."
"I seen that plane coming from my right and I just knew that thing was coming in too low. And if I would've stayed on the gas, I would've met it head on and it probably would've killed me."
Federal Aviation Administration spokesman Kathleen Bergen said the aircraft had departed from DeKalb Peachtree Airport, but ran into trouble shortly after take-off.
Federal investigators will have to reconstruct the plane in order to determine the cause of the crash. The reconstruction will take around two weeks, but a report on the cause can take between six months to a year.
Following the crash, the busy Interstate-285 was shut down in both directions.