Officials say fire crews arrived at the three family apartment building on East 225th Street in the Edenwald area at 5:20.
They removed a 60-year-old man and a woman from the burning building.
The man died at the hospital a short time later.
The woman is listed in stable condition at Jacobi Hospital.
Heavy smoke conditions may have hampered their escape from the building.
"The fire was under the garage which has a concrete floor. That holds everything in, the heat, smoke, so it stayed very smoky. We had to cut a hole in the first floor to get the smoke out," FDNY Battalion Chief George Campbell said.
All of the other residents made it out safely.
A firefighter and a police officer suffered minor injuries.
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