The wind-swept blaze spread quickly through three wood-frame buildings.
Several other families living in the attached, multiple-family dwellings managed to flee to safety, despite the fierce flames and acrid smoke - including a mother who neighbors saw break a window to get her youngsters out.
But the dead couple, who were in their 20s, couldn't break a window to escape said witness Pete Clare.
"People on the street were yelling, 'There's people in there!' " Clare said.
"I looked up and I saw these little hands trying to grab through a window - the hands looked like they belonged to a small child. We were trying to throw rocks to break the window."
The third-floor bathroom window at 36 Orchard St. overlooked a narrow alley. Two of the victims were found in the bathroom.
"I broke down and cried when I heard they died," Clare said.
The victims, whose names were not released, had emigrated from Mexico, a city official said.
Theodora Pierce heard a man screaming, "Fire! Fire!" while she was baby-sitting her grandchildren in her apartment a floor below.
"I just grabbed my two grandkids and ran out barefoot," she said.
"We barely made it across the street when flames just shot up the side of the building."
The man whose warning shouts saved her was Clare's brother-in-law, Alex Vazquez, who was moving into a first-floor apartment in the building with his family when the fire started.
Vazquez was carrying a TV into his apartment "when he opened the door and saw nothing but flames and smoke and [his daughter and mother-in-law] ran out," said his sister-in-law, Brandy Poncurak.
"He ran up to the second floor to get a fire extinguisher to try to put the fire out," but soon had to quit and run for his life, she said.
Third-floor resident Bernabe Ramos, 20, said, "I heard children screaming. They were desperate screams."
The four-alarm blaze was reported at 4:43 p.m. and took three hours to bring under control.
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