"The next time the Syrians use their air defense systems against our airplanes, we will destroy all of them without thinking twice," Avigdor Liberman said Sunday on Israeli public radio.
On Friday, Syria fired anti-aircraft missiles at Israeli military jets.
Israel says the four jets targeted a weapons shipment to Iran-backed Hezbollah but the Syrian military said the jets struck a military site near Palmyra. Israel said it was "absolutely untrue" that Syria's missiles downed one jet.
Syria accused Israel of supporting the Islamic State.
"Our central problem, and this above and beyond all of the other issues, is the transfer of advanced weapons from Syria to Lebanon," Liberman said. "Every time we identify a transfer like this, we will work to prevent the transfer of game-changing weapons. On this issue there will not be any compromise."