The cargo plane had left the US Manas airbase near the capital Bishkek, officials told AFP.
The aircraft came down near the village of Chaldovar, about 160km (100 miles) west of the US Transit Center at Manas, the Kyrgyz emergencies ministry said.
The emergency situations ministry said the plane had broken into three pieces but information about casualties has yet to be released.
Seven crew members died when a US civilian cargo plane crashed at Bagram airbase in Afghanistan on Monday.
Witnesses of the Kyrgyzstan crash told local media that they heard a boom and saw an explosion.
The transport plane was carrying a cargo of fuel when it disappeared off the radar near the mountain village of Chaldovar, close to the border with Kazakhstan, Reuters reported.
Rescue services went to the scene, a spokesman for the emergency situations ministry said.
However, local media reported that fire engines were struggling to reach the wreckage due to the mountainous terrain.
The US military uses the Manas airbase to maintain its operations in Afghanistan.
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