The train failed to stop as it pulled into Hoboken station at speed, went up over the blocks at the end of the track and rammed into a wall a few meters away, a New Jersey transit official told AFP at the scene.
Michael Larson, another transit employee, told CNN he heard a "bomb-like explosion" as the train hit the bumpers with such force that it went airborne -- hitting the station's roof and causing it to partly collapse.
"It was going considerably faster than it should have normally been at the terminal," he said. "It went up and over the bumper block, through the depot... and came to rest at the wall by the waiting room."
Video and photos posted on social media showed major damage to the transit hub just over the Hudson river from Manhattan, with the train tangled in wires and debris from what appeared to be caved in portions of the roof.
Train #1614 was arriving from Spring Valley when it struck the Hoboken terminal building at around 8:45 am (1245 GMT), New Jersey Transit said in a statement, adding that all services were currently suspended in and out of the station.
Passengers quoted by US media described the train ramming at full speed into the bumper at the end of the track.
"We never slowed down," Jim Finan, a commuter from New Jersey, told Fox News. "We ploughed, I mean, right through the bumper."
NBC and CBS reported three fatalities from the early morning accident. No official toll was immediately available.
"We have 100 plus injuries," Jennifer Nelson, a New Jersey transit spokeswoman, told reporters at the scene, adding that there were "multiple critical injuries."
Nelson said there were around 250 passengers on board at the time of the crash, and that it was not known if there were still people trapped on the train.
Finan said it was an unusually crowded morning.
"Afterwards there was some panic. People were trying to smash some windows out."
"Everyone who was standing kind of went flying," he said. "I saw a lot of head injuries and kind of people with cuts."
'Pretty chaotic'
Nelson told reporters it was not known how fast the train was travelling as it entered the station, and that an investigation was ongoing.
"We're looking at all things that could have caused this accident," she said.
Emergency vehicles converged on the scene in response to the crash.
Pancho Bernasconi, Getty's director of photography for news who arrived at the station just after the crash, told AFP he saw people running for shelter, several of them injured.
There was "a lot of damage" to the station. "Part of the roof has collapsed."
Passengers described a scene of chaos with dazed and bloodied people making their way to safety.
"We crashed, and the lights went out. A few people screamed," Leon Offengenden told CNN.
"It was pretty chaotic. And people just in shock and everybody has photos and cameras out and iPads. It was pretty intense," he said.
The last major train crash in the United States was in May 2015, when an Amtrak train linking Washington to New York derailed in Philadelphia, leaving eight dead and 200 injured.
In December 2013 in New York a suburban train derailed in the Bronx while travelling at several times the speed limit, leaving four people dead and more than 60 injured.