Iran, along with Russian Federation, has provided crucial support to Syrian President Bashar al-Assad during Syria's civil war, which began with a violent government crackdown on protesters in March 2011.
The targets included surface-to-air missiles, headquarters, weapons depots, and military bases, Israel's military spokesperson Lt. Col. Avichay Adraee said on Twitter.
The British-based Syrian Observatory for Human Rights (SOHR) that monitors the fighting reported that 11 people, including seven non-Syrians (Iranians), were killed in the attacks.
IDF forces took swift action to neutralize the threat.
Two of the missiles separately destroyed two "residential buildings" in the towns of Saasa and Qudsaya, killing two civilians and injuring several others, the source added.
A military statement was released by state news agency SANA that Israeli warplanes from the occupied Golan Heights and the Lebanese Marj Oyoun area targeted the vicinity of Damascus with a number of missiles, adding that most of the missiles were intercepted.
While Syria's air defenses were able to destroy most of Israel's missiles, SANA said three people were injured as a result of the attack.
The next level of escalation might involve strikes against Iran's ancient American-made F-4s, which they are trying to upgrade.
Tensions on Israel's northern border with Syria have been running high in the a year ago with several incidents between forces of the two countries.
"Iran is continuing to test Israel's boundaries", said Menahem Merhavy, an expert on Iran at the Harry Truman Institute at the Hebrew University in Jerusalem.
While Israel faces tensions with Iranian proxies along its borders, Iran's regional influence is also being challenged by unprecedented, economically-driven mass protests in Iraq and Lebanon - two countries where Tehran wields major influence. The protests were sparked by a spike in fuel prices.
Moreover, Israeli Prime Minister Benjamin Netanyahu said Wednesday that Israeli authorities carried out the strike on Syria to demonstrate that the country will respond to any hostile acts against it. "That is what we did tonight toward military targets of the Iranian Quds Force and Syrian military targets".
"The rules have changed: whoever fires on Israel during the day will not sleep at night", he said.
"Our message to the leaders of Iranian is simple: You are not immune anymore. Any place you dispatch your tentacles, we will chop them off".
The rare rocket fire comes a week after an Israeli airstrike against a top Palestinian militant based in Syria.
Netanyahu has said repeatedly that he will not allow Iran to establish a frontline against Israel in Syria.
Video footage from Syria appeared to show a Syrian air defense missile crashing to the ground in a heavily populated area shortly after launching, which may account for some of the casualties.