At least 200 firefighters are battling the blaze that sent large plumes of dark smoke across the city from where it started in Hamilton Heights.
The blaze broke out earlier this morning on the top floor of a building located at 144th Street and Broadway.
The Fire Department of NY says 170 firefighters are at the scene. Two have reportedly suffered non-life-threatening injuries.
Heavy smoke and orange flames could be seen pouring through the building's roof, with strong wind making the blaze hard to contain.
Dozens of people, including residents and store owners, have lined the streets of the hectic scene. Local media reports the fire quickly spread through the six story building which has retail shops on the first floor and apartment units on the other floors.More news: Ohio Supreme Court Justice Defends Controversial Facebook Post As "Appropriate"
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"Upon arrival we found very heavy fire conditions on the top floor".
According to Zillow.com, the residential building was built in 1918.
Authorities urged pedestrians to stay away from the area after pieces of the building began falling onto the street after the roof collapsed.
Although officials had earlier feared it would collapse, the structure was now stabilized, he said. Emergency workers evacuated the burning building and the nearby buildings as a precaution. Many residents were visibly upset as they realized their homes were completely destroyed.