The plane - an internal flight from Newark, New Jersey, to Buffalo, New York State - came down at around 10.20pm last night (local time) in Clarence, a residential area five miles away from its airport destination.
Despite taking a direct hit, two people living in the property - a mother and daughter - escaped with minor injuries. But a man inside was killed.
A police spokeswoman said it was "amazing" that the damage was limited to only one house. An emergency co-ordinator said that the plane could have "wiped out" the entire neighbourhood.
Air accident investigators were today on the way to the scene of the crash, the US's first fatal incident involving a commercial airliner for two-and-a-half years.
Following the accident, at least two pilots were heard on air traffic control talking of having ice on their wings.
"We've been getting ice since 20 miles south of the airport," one said.
It is believed that it will take a number of hours before the site is safe enough for investigators to start their work trying to establish what went wrong.
Air traffic control received no mayday report warning ahead of the plane coming down. Neither the pilot nor controller showed any signs of distress before the jet went off the radar.
The Department of Homeland Security said there was no indication that terrorism was involved.
Locals have reported hearing an unusual noise from the plane seconds before it came down.
David Luce said: "It didn't sound normal. We heard it for a few seconds, then it stopped, then a couple of seconds later there was this tremendous explosion."
Twelve homes were evacuated as firefighters battled the resulting fireball. The impact killed all 44 passengers, four active crew members and one off-duty flight staff on board the 74-seat Continental Connection Flight 3407.
Among the dead was a widow of the 9/11 attack on the World Trade Centre.
Those in the house who survived, Karen Wielinski, 57, and her 22-year-old daughter Jill - were taken to hospital for treatment for minor injuries.
Dave Bissonette, an emergency control director in Clarence, said that it appeared that the plane "dove" directly into the top of the house.
He added: "It is remarkable that it only took one house. As devastating as it was, it could have easily wiped out an entire neighbourhood on a strafing run type of thing."
New York State police spokeswoman Rebecca Gibbons said: "The fact that the damage is limited to the one residence is really amazing."
Nearby resident Tony Tatro was driving home from the gym when the plane passed directly overhead.
He told CNN: "The plane was nose down and steep enough so that it did not look right. It was about 75ft above me.
"Had it been on a flatter trajectory, it would have hit more than one house - it was relatively steep."
In a statement from the White House, President Barack Obama said he was "deeply saddened" to hear of the accident.
He added: "We pray for all those who have been touched by this terrible tragedy to find peace and comfort in the hard days ahead."
Officials said relatives of passengers aboard the flight should call 1-800-621-3263 for information.