Albanian officials said the C-130 transport plane struck a mountain after apparently flying too low in an uninhabited region near the town of Gramsh, 150km south of the Albanian capital Tirana.
"Nine Americans were on board the aircraft and they probably haven't survived," said Albanian defence ministry spokesman Agim Doci.
The US embassy and Nato officials in Tirana would not comment on the crash.
Rescue operations were hampered by snow which made access difficult.
A US plane and Albanian helicopters were sent to the crash site but had problems landing. It would take up to four days to reach the area by foot.
The plane had taken off from Tirana's Rinas military base and was to monitor the mountainous region in the south of the country.
The Albanian news channel News 24 said Brindisi airport in southern Italy, which operates a Nato radar, picked up a distress signal from the stricken aircraft.