Eric Phillips, a spokesman for Mayor Bill de Blasio, said in a post on Twitter there was "at least one survivor, at least two fatalities".
The New York Post described the chopper as a "tour helicopter", and reported it plunged into the river near Gracie Mansion.
New York City Police Commissioner James O'Neill said the aircraft was registered to Liberty Helicopters, a sightseeing and charter service in New York, and was on a private charter "photo shoot".
"It kind of hit sideways and just flipped over", Brianna Jesme, 22, an Upper East Side resident who witnessed the crash, told Reuters TV. "The other five did not", FDNY Commissioner Daniel Nigro said in a news conference Sunday night. "By the time we got out here, we couldn't see it".
The skies over NY constantly buzz with helicopters carrying tourists, businesspeople, traffic reporters, medical teams and others.
Police are advising drivers to expect heavy traffic and emergency personnel in the area.
Twitter footage captured the moment a helicopter crashed into the East River.. Three other passengers were injured. In June 2005, two helicopters crashed into the East River in the same week.
The cause of the crash is unknown.
The National Transportation Safety Board is investigating the incident.