Firefighters were forced to rescue them through the windows.
The fire started in a kitchen of the apartment on 65th Avenue in Fresh Meadows just before 2 a.m., and officials say the situation could have been much worse if not for working smoke detectors.
Authorities say the family members - two parents and two children - were trapped in their bedrooms by the heavy smoke and began to lose consciousness.
Firefighters extended ladders to the second-floor windows and pulled out at least eight residents.
"I think within five minutes, rescuing the people and putting the fire out pretty quickly," FDNY Deputy Chief Mark Ferran said. "And again, it's the smoke that's the major source of the injuries."
The mother and a 3-year-old were taken to Long Island Jewish Hospital, while the father and 14-year-old were taken to New York Hospital Queens. All four were listed in critical condition. The others, including one firefighter, suffered non-life-threatening injuries.
"I actually heard the alarms going off, and she was screaming upstairs," resident Susan Abdurakhmanov said. "It all started from upstairs."
The 16 residents of the house were left homeless.
The cause of the fire is under investigation. It was deemed to be accidental.