At least 200 firefighters responded to the blaze, which broke out on the second and third floors of a 19-story building in The Bronx.
According to witnesses, trapped residents screamed for help from windows during the deadly inferno. The city's fire chief said that the fire caused by a portable electric heater, leaving victims on every floor.
A 38-year-old Dilenny Rodriguez, who escaped with her children told AFP that there were a lot of kids crying, 'Help! Help! Help!'
According to the report, Mayor Eric Adams said that 19 people had been confirmed dead and 63 had been injured, including several that were in a critical condition.
He said that this is going to be one of the worst fires in the history.
The Mayor in a another tweet said, "Join me in praying for those we lost, especially the 9 innocent young lives that were cut short."
The mainly working class borough of The Bronx is home to a large number of immigrants and Adams said "many" of the building's residents had been Muslims who moved to New York from Gambia.
Photographs and video posted on social media showed flames and thick black smoke billowing out of a third-story window of the brick building at East 181st Street as firefighters operated on a nearby ladder.
"The fire alarm of course started and then, everywhere was smoke," said Mohamed Trawalley, 49, a resident of the building.
"So it was definitely devastating. A lot of smoke. Until now, when I clear my throat, all I see is black mucus. It was so serious, I've never seen anything like it before."
"It was chaos," George King, who lives directly adjacent to the building, told AFP.
"I've been here 15 years and it's the first time I've seen something like this.
The injured were taken to five hospitals; many suffered from cardiac and respiratory arrest and severe smoke inhalation, officials said.
New York City Fire Department Commissioner Daniel Nigro told reporters that the fire started in a bedroom in a portable electric heater.
He said that flames quickly engulfed much of the structure and that the smoke was so dense as to be "unprecedented."
Nigro added that "very heavy" fire and smoke "extended the entire height of the building."
"Members found victims on every floor, in stairwells," he said.
"The last time we had a loss of life that may be this horrific was a fire which was over 30 years ago, also here in the Bronx," Nigro added.
He explained that the fire originated in a duplex apartment on the second and third floors of the building.
