Israel fears an eventual Assad victory could leave Iran with a permanent garrison in Syria, extending a threat posed from neighboring Lebanon by the Iranian-backed Hezbollah.
Meeting Putin in the Black Sea resort of Sochi, Netanyahu said Iran was fighting to cement an arc of influence from the Gulf to the Mediterranean.
"Iran is already well on its way to controlling Iraq, Yemen and to a large extent is already in practice in control of Lebanon," Netanyahu told Putin.
"We cannot forget for a single minute that Iran threatens every day to annihilate Israel," Netanyahu said. "Israel opposes Iran's continued entrenchment in Syria. We will be sure to defend ourselves with all means against this and any threat."