At least 10 people, including five Iranians, were killed in the military action, according to the Syrian Observatory for Human Rights. While Israel has repeatedly attacked targets in war-torn Syrian in recent years, it rarely publicly acknowledges it.
Its latest manoeuvres send a clear signal to the world that it will pursue its policy of striking across the border despite the election defeat of US President Donald Trump.
Syrian state media said three Syrian soldiers were killed and another injured.
The Observatory said the dead Iranians were members of the elite Quds Force.
The group is a branch of Iran’s Islamic Revolutionary Guard Corps and specialises in unconventional warfare and military intelligence operations.
The monitor also said at least two Lebanese or Iraqi Shi’ite militiamen lost their lives in the attacks.
A commander of pro-Damascus forces denied Iranians or Lebanese were among the casualties.
Israel said it was retaliating for what it called an Iranian-sponsored operation in which Syrians planted explosives near an Israeli military base in the occupied Golan Heights.
Lieutenant-Colonel Jonathan Conricus, an Israeli military spokesman, said eight targets were hit.
A former Syrian military commander claimed the attacks also targeted bases of the Iranian-backed Lebanese Shi’ite group Hezbollah in Syria.
This was not mentioned by Lt Col Conricus.
Israel has this year stepped up its attacks against Iranian-linked targets in Syria.
Western intelligence sources describe this as a shadow war to reduce Iran’s influence in the troubled region.
Wednesday’s attacks struck a far wider range of targets than usual.
Mr Trump has been a strong backer of Israeli military intervention against Iranian forces in Syria.
President-elect Joe Biden has said he will try to revive a nuclear agreement with Iran that Mr Trump abandoned.
Following the strikes, Israeli Intelligence Minister Eli Cohen said on Army Radio: “Biden has to ask himself, exactly what is Iran after in Syria?”
Syrian President Bashar al-Assad’s government has never publicly acknowledged that there are Iranian forces operating on his behalf in Syria’s civil war, only that Tehran has sent military advisors.