Fire officials said the fire started around 1:15 a.m. inside a garden apartment on the north side of the building, which is located in the 8000-block of South King Drive in the city's Chatham neighborhood.
The smoke and flames spread fast as crews worked to rescue several people from the top floors. Several apartments were heavily damaged, leaving people displaced.
"Two o'clock in the morning, and you out here, no place to lay your head. You're done. So what are you going to do?" asked Douglas Samuels, who lived in the building.
Two residents were taken to the hospital in serious condition. One firefighter suffered a minor injury.
The fire was extinguished by around 2 a.m. The cause remains under investigation.