A senior Israeli source said the aerial assault hit Iranian weapons destined for the Lebanese militant group Hezbollah, which is allied to the Syrian regime.
And a diplomatic source in Beirut told AFP three sites were targeted -- a military facility, a nearby weapons depot and an anti-aircraft unit in Sabura, west of the capital.
The official SANA news agency said Israel had targeted the military research centre at Jamraya, northwest of Damascus, without giving details on casualties or damage.
"This new Israeli aggression is a clear attempt to alleviate the pressure on the armed terrorist groups after our army beat them back in several regions and after the army's victories on the road to recovering security and stability in Syria," SANA said.
The Israeli strike "opens door to all possibilities," said Syria's information minister Omran al-Zohbi at a press conference broadcast live on state television.
The Israeli strikes were staunchly condemned by Egypt as a "violation" of international law while the Cairo-based Arab League demanded UN Security Council intervention to stop such Israeli attacks.
The Israeli source, speaking on condition of anonymity, said the target "was Iranian missiles which were destined for Hezbollah".
He also confirmed Israel was behind an attack overnight on Thursday, which sources told AFP targeted a weapons storage facility at Damascus airport.
"This attack proves the direct involvement of the Israeli occupation in the conspiracy against Syria and its links with terrorist groups in the aggression supported by Western countries and some Gulf countries," SANA said of the latest strike.
Residents of the upscale Damascus neighbourhood of Dumar said the earth shook violently and turned the black night sky red.
"It was like an earthquake, the sky was yellow and red," said 72-year-old Najwa.
Video footage uploaded to YouTube appeared to show a series of missiles lighting up clouds, blazing fires and an explosion producing an orange fireball that momentarily fills the screen.
The powerful blast sent up towering clouds of smoke illuminated by burning debris.
If confirmed, the attack would be Israel's second this week against targets inside Syria and the second time it has targeted the Jamraya facility, after a January 30 raid that Israeli officials implicitly acknowledged.
On Sunday, Israeli Prime Minister Benjamin Netanyahu delayed his departure on a trip to China by two hours, reportedly to attend a security cabinet meeting.
Israel has frequently warned that it would act to stop the transfer of advanced weapons systems or chemical weapons to Lebanon's Hezbollah with which it fought a devastating war in 2006.
Hezbollah and Iran, the regional arch-foes of Israel, have steadfastly backed the regime of Syrian President Bashar al-Assad since the uprising against it erupted in March 2011.
Iran's defence minister General Ahmad Vahidi said "the assault, which was carried out with the US green light, unveils the links between the terrorist mercenaries and their masters of the Zionist regime."
Britain warned of the risk to the region posed by the Syrian conflict, which is now in its third year and has killed more than 70,000 people.
"These events, and many other events of recent days, do show increasing danger to the peace of that entire region from the Syria crisis just getting worse and worse," British foreign secretary William Hague said.
US President Barack Obama, speaking after the first reported attack this week, said Israel was justified in protecting itself.
"The Israelis justifiably have to guard against the transfer of advanced weaponry to terrorist organisations like Hezbollah," he said, without commenting directly on the strike.
"We coordinate closely with the Israelis, recognising that they are very close to Syria, they are very close to Lebanon."
The rebel Free Syrian Army reacted cautiously, saying their country was already under daily attack by regime aircraft.
"Of course the Free Syrian Army and any Syrian is bothered that their country is being bombed, but Syria is being bombed every day by Bashar al-Assad, and by Israel," the FSA's Louay Muqdad told AFP.
The strikes came shortly after the Syrian Observatory for Human Rights reported the bodies of at least 62 people had been found in a Sunni district of the port of Banias, a day after a regime assault.
The opposition National Coalition warned that the deaths were part of "a proliferation of massacres that is transforming into an ethnic cleansing operation like that carried out by Serbian forces in Bosnia 20 years ago".
Elsewhere in Syria, the Observatory reported regime air strikes against the Damascus neighbourhood of Jubar and the rebel-held town of Raqa.