"Our C-130 military cargo plane, which took off from Azerbaijan to return home, has crashed at the Georgia-Azerbaijan border," the ministry said in a statement, confirming there were "20 personnel on board, including the flight crew".
Search and rescue operations were ongoing, it added.
Dramatic footage circulating in Azerbaijani media appeared to show the plane spinning horizontally as it fell out of the sky, sending up a large cloud of black smoke after crashing.
Footage said to be from the crash site purportedly showed the blackened wreckage burning as several bystanders watched in a field.
Turkey's defence ministry asked the press not to publish images of the crash.
President Recep Tayyip Erdogan said Turkey was working with the Georgian authorities "to reach the wreckage", expressing sorrow "for our martyrs", according to the Anadolu state news agency.
In a post on X, Azerbaijan's President Ilham Aliyev extended his condolences to the Turkish leader.
Foreign Minister Hakan Fidan also spoke by phone with his Georgian counterpart Maka Bochorishvili about the search and rescue operations, the ministry said in a statement.
Georgia's interior ministry confirmed the plane went down in the Sighnaghi area, "about five kilometres (3.1 miles) from Georgia's state border" with Azerbaijan.
Georgia's Sakaeronavigatsia air traffic control service said the plane had disappeared from radar shortly after entering Georgian airspace, and that it had been alerted to the crash by emergency services.
"A Turkish C-130 aircraft disappeared from Sakaeronavigatsia's radar a few minutes after entering Georgian airspace, without transmitting a distress signal," it said in a statement, saying it had initiated "search and rescue operations".
"The airport in Ganja, Azerbaijan -- from which the Turkish aircraft had departed -- has been notified, as has the Turkish side," it added.
The C-130 Hercules military cargo plane is made by US manufacturer Lockheed Martin.
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