The fire erupted shortly after 4 a.m. at a three-story building in the 800 block of North Bunker Hill Avenue, officials said. The fire was believed to have started by homeless encampments.
"There have been several fires at this structure here. And they come out and they put it out, the police chase the homeless out, but they keep coming back. So this time, they set it good," said resident Ken Ferris.
Video from AIR7 showed dramatic flames spewing from the upper floors of an adjacent building and through the roof after the fire engulfed the original building.
With over 130 firefighters at the scene, the fire was extinguished shortly before 5:30 a.m.
An 80-year-old man was rushed to an area hospital in critical condition, while a 55-year-old woman was taken to the hospital with a non life-threatening burn injury, fire officials said. Dozens of people were displaced and were receiving help from Red Cross personnel, officials said.
The fire remains under investigation.