Emergency services are on the scene and say four people are critically injured, and 12 others were injured.
Flames and smoke pouring out of a five-floor building, and firefighters are spraying the building.
Officials are investigating whether a gas leak is to blame. There were reports of an explosion before the fire.
About 250 fire-fighters are on hand to battle the blaze.
Emergency services started received calls reporting the fire around 15:15 local time.
According to the New York Times, an explosion triggered the fire in one building, which quickly spread to another.
The area in Manhattan’s East Village – close to New York University – is being evacuated.
Firefighters began spraying the flames, but had to retreat after the flames became too intense, the local station reported, local news station WABC reported.
The station said that there are fears that the other building could collapse as well, and it’s not clear if anyone has been trapped in the building or rubble.
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