The blaze was reported at about 3:18 a.m. in the 900 block of East 31st Street at a single-story commercial building, used as a garment factory.
While crews were on the roof trying to ventilate the blaze, a firefighter fell through to the floor below.
"Whenever you hear a firefighter through the roof, your heart drops, and you go into a hyper mode to do everything you can to recover him," said Assistant Chief Ralph Terrazas with Los Angeles City Fire.
When the call went out, fellow firefighters rushed into action. Fortunately, the firefighter had fallen in an area that was not burning. Surrounding firefighters inside the structure were able to locate and extricate him quickly.
Three other firefighters were also injured while battling the blaze.
All firefighters were transported to an area hospital in serious condition to be treated for non life-threatening injuries, said Katherine Main, public information officer for the Los Angeles Fire Department.
Fire officials say the situation could have been much worse.
"You can see the building literally swallowed this firefighter. If it wasn't for his training, his ability to stay calm and his dependence on his personal protective equipment, we would be talking about a fatality here," said Captain Jaime Moore with Los Angeles City Fire.
A total of 65 firefighters successfully knocked down the blaze at about 5 a.m. The cause of the fire remains under investigation. Arson investigators were combing through the charred wreckage. It appears the fire started at the back of the building.