The flames broke out on the second floor of 293 East 8th Street in the Kensington section just before 5:30 a.m. The fire quickly spread to the third floor, and the blaze went to a second alarm about a half hour later.
Firefighters were on the scene within minutes and worked to get the fire under control.
All three victims were found unresponsive in a third-floor bathroom. The 16-year-old girl died, while her 27- and 24-year-old sisters were rushed to the hospital with life threatening injuries.
The 27-year-old woman is in critical condition at the burn unit at Weill-Cornell Medical Center, while the 24-year-old is critical at Kings County Hospital.
The women's 57-year-old mother and her 59-year-old sister were able to escape with minor injuries. They are in stable condition at Kings County Hospital being treated for smoke inhalation.
The cause of the fire is under investigation, but firefighters say there were no working smoke detectors in the home.