Metropolitan Transportation Authority police say the train derailed near the Spuyten Duyvil station just after 7.20am.
Pictures showed five carriages lying on their side, with one inches from the Hudson river.
The derailed train was the 05:54 service from Poughkeepsie, in upstate New York, which was due to arrive at Grand Central Station in Manhattan at 07:43.
It left the tracks in the Spuyten Duyvil section of the Bronx. The area, whose name translates from the Dutch to "Spitting Devil", is known for its difficult curved section of railway line and was the scene of a 10-carriage garbage train derailment only four months ago.
The fire department says 130 firefighters are on the scene.
A passenger calling himself Frank, who was in the carriage that ended up on the edge of the water, told the local ABC News channel that several people from the carriage were "leaving on a stretcher". He was on his way to the hospital with minor head and neck injuries, having climbed out.
Edwin Valero was in an apartment building above the accident scene when the train derailed. He says none of the cars went into a nearby body of water, but at least one ended up a few feet from the edge.
Sunday marks the end of America`s Thanksgiving holiday, which annually sees many people take time off to enjoy a long weekend and travel home to their families across the United States.
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