The flames broke out at a three-story multi-family dwelling on East 35th Street in the Flatbush section around 4 a.m. and quickly spread to three alarms.
There were several people inside at the time, but all of them managed to escape safely except for one person who needed to be rescued from inside a bathroom on one of the upper levels.
Firefighters were able to get to the disabled woman and pull her to safety.
She refused medical treatment at the scene, while two firefighters were treated for smoke inhalation.
Firefighters extinguished the blaze within two hours, but were still working on hotspots and making sure all the fire was out.
"The fire started on the first floor and then went to both the second and third floor," FDNY assistant chief Joseph Pfeifer said. "A little while later, because of the volume of fire, we transferred to a third alarm. So there was about three dozen units here and about 100 firefighters."
Firefighters were concerned the flames would spread to neighboring buildings, which brought about the massive effort.
The cause of the fire is under investigation.