The 3-alarm fire broke out at about 4 a.m. in a two-and-a-half-story house on 44th Street in Borough Park.
Firefighters encountered heavy smoke and flames on the first floor. By the time they got inside, the fire had spread to the second floor.
The victims were found unconscious in a back bedroom. Both were pronounced dead at Maimonides Hospital.
Police identified the fatal victims as 61-year-old Howard Gluck and 59-year-old Evelyn Gluck.
Their 17-year-old daughter is in stable condition.
The cause of the blaze remains under investigation.