State police spokeswoman Rebecca Gibbons told US media that there were 48 people on the plane and "there were no survivors." A county official had earlier confirmed one fatality on the ground.
An Erie County official said Continental Airlines flight 3407 crashed at 10:20pm (0320 GMT) in the town of Clarence Center, New York, about five minutes before it was due to land at the Buffalo airport.
"One structure has been seriously damaged and the aircraft is currently still burning – somewhat under control," David Bissonette, emergency coordinator in Clarence Center told reporters. "We have multiple fatalities. The scene is secured by the state police and a long-term investigation is imminent."
One county official said he was not aware of any reports of trouble from the plane.
"I was told the plane simply dropped off the radar screen," the official said.
US media showed footage of the smoking wreckage in the center of a residential neighbourhood.
A man who gave his name only as Tony told a local television station that the plane flew right over his car, "nose down."
"Left wing was slightly down, pitched sideways, if you will," he said. "It was on a direct line down."
David Luce, who lives about 150 yards (meters) from the crash scene, told the Buffalo News he heard a huge explosion and saw flames 40-50 feet in the air.
"It sounded quite loud, and then the sound stopped," Luce said. "Then one or two seconds later, there was a thunderous explosion. I thought something hit our house. It shook our whole house."
"There was the initial boom, and then these cannon shots ... these loud secondary explosions, and they went on for about 10 minutes."
After a few minutes, Luce said he walked out to take a look at the wreckage and saw the house was destroyed.
"The house was already flattened. There was no house, just a pile of rubble and still burning," he said.