The Israeli military said its Iron Dome rocket defense system intercepted some of the incoming projectiles, while others caused only minimal damage.
United Nations Security Council Resolutions have demanded the return of the Golan Heights to Syria, but Israeli leaders have made it clear they have no intention of conceding the strategic position to Syria.
The extent of the damage inflicted by the Israeli airstrikes was not immediately clear. Israeli officials have been envisioning the end of the deal leading to regime change in Iran, and have also advocated a war to impose regime change. The incoming attack set off air raid sirens in the Israeli-controlled Golan, which was captured from Syria in the 1967 war.
Avigdor Lieberman says Thursday Israel responded fiercely to an unprecedented rocket attack by Iranian forces in Syria against Israel.
"This event is not over", he said.
Syrian state media said dozens of Israeli missiles hit a radar station, Syrian air defense positions and an ammunition dump, underscoring the risks of a wider escalation involving Iran and its regional allies.
Syrian activists reported Israeli airstrikes hitting targets near Damascus. One video posted online showed a large explosion and shrapnel flying in the air.
In the past, Israel and Iran fought the war between them via their proxies.
Russian Federation says the Israeli strikes on Iranian facilities in Syria have marked a risky escalation, urging both Israel and Iran to avoid provoking each other.
"The holy system of the Islamic Republic will step up its missile capabilities day by day so that Israel, this occupying regime, will become sleepless and the nightmare will constantly haunt it that if it does anything foolish, we will raze Tel Aviv and Haifa to the ground", he said, according to state television. Al-Ikhbariya TV said missiles targeted 10 Israeli positions.
Syrian media said it was the first time in years that Syrians had fired at Israeli forces in the Golan Heights.
Hours before Trump's announcement, Israel went on high alert upon identifying "irregular activity" by Iranian forces in Syria.
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Israel attacked dozens of suspected Iranian targets in Syria in overnight strikes this week that it said were in response to an Iranian rocket barrage.
Last month, an attack on Syria's T4 air base in Homs province killed seven Iranian military personnel.
Israel regards Iran as its biggest threat, and has repeatedly targeted Iranian forces and allied militia in Syria. Israel's response was massive.
"We do not know yet the (Iranian) casualty count", he said.
In February, Israel shot down what it said was an armed Iranian drone that entered Israeli airspace.
Israel anxious installation of the defense systems could upset the balance of power in Syria and could make Israeli aircraft penetration more hard.
In an attempt to explain the situation, Bahrain's Foreign Minister Sheikh Khalid al-Khalifa said on Twitter, "Since Iran violated the status quo in the region and violated countries' (sovereignty) via their forces and missiles, then any country in the region, including Israel, has the right to defend itself by destroying the sources of threat".
But the Syrian war has given Tehran the possibility of opening up an additional direct front against Israel on its northern border.
The reports of an Israeli attack in Kisweh late on Tuesday emerged after US President Donald Trump announced he was pulling out of the Iranian nuclear deal.
Israeli Prime Minister Benjamin Netanyahu was a sharp critic of the Iran nuclear deal.
Iran has advisers and experts and has backed tens of thousands of militiamen who are fighting alongside Assad's forces in the civil war.
But if they do escalate, the region could face one of its worst cross-border conflicts in decades, one that could potentially drag in the United States, a major ally of Israel, and Russian Federation, which is Syria's mightiest ally.