The fire tore through a three story brownstone, with a religious store on the first floor and apartments above.
Two of the residents, who were most seriously injured, were rescued from the second floor and pulled onto tower ladders.
All five residents were taken to Methodist Hospital for treatment. The two more seriously injured and the other three are being treated for smoke inhalation.
The two firefighters were treated at Long Island College Hospital for minor injuries.
Fire marshals are investigating the cause.