It fell in the buffer zone between the Israeli- and Syrian-controlled parts of the Golan.
The drone was launched from an air base near Damascus and was downed with a Patriot interceptor missile over the Golan demilitarized zone that has separated Israeli and Syrian forces since the ceasefire deal that followed their 1973 war, the military said.
"The IDF will not allow any infiltration or attempt to infiltrate Israeli airspace by any Iranian terror group, be it Hezbollah or Shia militia groups".
The IDF will act severely and attack against any such actions, said Manelis, adding: "We will respond to every such attempt".
Israel carried out a test of the Patriot missile system in August, in response to the threat posed by drones entering Israeli airspace.
Following the incident the army raised the threat level in its Northern Command.
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The Israel Air Force's aerial defense command fired a Patriot missile and destroyed the drone.
Israel seized 1,200sq/km of the Golan Heights from Syria in the Six-Day War of 1967 and later annexed it in a move never recognised by the worldwide community.
According to an IDF spokesman, the drone was being used by Hezbollah militants for the reconnaissance purposes.
"Hezbollah has over 10,000 fighters deployed in southern Syria. This wealth, which rightly belongs to Iran's people, also goes to shore up Bashar Al Assad's dictatorship, fuel Yemen's civil war, and undermine peace throughout the entire Middle East".
"The transition from routine to emergency at a pace that we are living here is unprecedented, and I repeat that there is no more army more prepared, at a professional level like the IDF".
Israel shot down a pilotless aircraft that tried to enter its airspace at its Golan Heights frontier with Syria on Tuesday, the IDF said.