The chopper was said to be "flying erratically" before it crash landed on the AXA Equitable Center building on 7th Avenue, which is close to the Empire State Building and Times Square.
The twin-engine, lightweight Agusta A190E was also in restricted airspace, where aircraft are forbidden from flying below 3,000ft (914 metres) within a one-mile radius of Trump Tower.
The tower is just a few blocks from the site of the crash.
Authorities say the helicopter had taken off from a pad on Manhattan's east side at 1.32pm local time, and had crashed on the skyscraper just 11 minutes later.
The pilot has been named as Tim McCormack, who worked for Daniele Bodini, founder of the real estate firm American Continental Properties Group.
He had been intending to land at Linden Airport in New Jersey, according to Paul Dudley, the airport's director.
Mr Dudley said: "Tim McCormack is a well-respected, highly trained veteran pilot who also had tremendous local knowledge, having flown in this area for many years.
"We're all saddened and shocked."
No other injuries were reported.
New York Governor Andrew Cuomo arrived at the scene shortly after the incident, and offered reassurances to those who were reminded of the September 11 terrorist attacks.
"If you're a New Yorker, you have a level of PTSD from 9/11," he said.
"I remember that morning all too well. So as soon as you hear an aircraft hit a building I think my mind goes where every New Yorker's mind goes." But, he added, there were no suggestions of a terror attack.
Donald Trump, who said he had been briefed, praised the "phenomenal job" carried out by emergency services, and those still at the scene.
In a further statement, the US president described the crash as a "big tragedy" and a "very, very sad event".
He added: "The federal people are working with the city and state people and they'll have a full report very soon."
The skyscraper was evacuated after the crash, with many of those inside describing how the building shook as the helicopter made impact.
Nathan Hutton, who works on the 29th floor, said: "It felt like you were just standing there, and someone takes their hand and just shoves you.
"You felt it through the whole building."
Another witness who was also in the building at the time told ABC News: "You could smell the smoke coming down from the upper floor and it smelled like burning construction material."
He added: "When we got to the first floor… that was when we were told, 'Everybody get out now'."
Meanwhile, an umbrella seller on the street below said he heard a "rumble".
He said: "I didn't see it, but I felt it. Smoke was on top of the building."
Emergency services blocked the streets with dozens of fire engines and police cars, and bystanders were warned to stay away as work continued to stop fuel leaking from the helicopter.
The weather in New York was wet and cloudy around the time of the crash, with one witness in an adjacent building describing the site as "very foggy".
The Federal Aviation Administration said the National Transport Safety Board (NTSB) would investigate the crash.
The NTSB has not yet responded to Sky News' request for comment.