The aircraft, a Colgan Air Bombardier Dash Q400, is believed to have been approaching Buffalo Niagara International airport amid sleet, snow and fog when it came down on a suburban street.
Al Jazeera's John Terrett said: "Firefighters had trouble getting near the wreckage as the heat from the fire was too great.
"Two people were taken to hospital. Both are said to have been on the ground at the time of the crash."
The aircraft hit a house and exploded at 10:10pm (0310 GMT). A county official told reporters "the plane simply dropped off the radar screen".
Several homes near the crash site were evacuated as firefighters sought to control the blaze.
Steve Barber, a reporter a WKBW Eyewitness news in Buffalo, said authorities were trying to keep the temperatures low at the crash site so that they can investigate.
"It does not appear at this point that [the crash] is weather related," he said.
"By Buffalo's standards the weather was not that bad - we were getting some light snow and it was pretty foggy, with winds of about 25 miles per hour."