Some 168 firefighters are dealing with a "multiple dwelling explosion and collapse" in the East Harlem area of the city.
The blast happened at around 9am local time on Wednesday morning.
It's not clear what the cause of the reported explosion was.
At least a dozen people have been injured, according to officials from the fire department.
It's understood debris on nearby train tracks has caused the halt of some services in the area.
One eyewitness told NBC "I thought a train had exploded".
"There are a ton of firefighters and a lot of smoke. Cops and first responders are everywhere," Marisa Aquino told the network.
According to WABC, witnesses reported seeing a "partial roof collapse".
It also said the structural integrity of the building may have been compromised.
One of those on the ground said she "thought she was going to die" and described the blast as feeling "like an earthquake"
It's understood the three buildings affected housed a church, shop and apartment complex.
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