State media said a research centre and other sites had been hit overnight. Israeli sources said weapons bound for Hezbollah in Lebanon were the target.
The strike, the second in two days, drew condemnation from the Arab League.
Syria's government refers to rebels fighting against it as "terrorists".
On Friday, Israeli aircraft hit a shipment of missiles near the Lebanon border, according to unnamed US and Israeli officials.
The BBC's Yolande Knell in Jerusalem says the latest developments are a significant escalation in Israel's involvement in the conflict.
"The Israeli attack led to the fall of a number of martyrs and wounded from the ranks of Syrian citizens, and led to widespread destruction in these sites and in the civilian districts near to them."
The statement added: "This leaves no room for doubt Israel is the beneficiary, the mover and sometime the executor of the terrorist acts which Syria is witnessing and which target it as a state and people directly or through its tools inside."
The Syrian cabinet held an emergency meeting on the attacks, after which Information Minister Omran al-Zohbi read a statement at a news conference.
He said the attack made the Middle East "more dangerous" and "opens the door wide to all possibilities".
Syria had the right and the duty "to defend its people by all available means," he added.
'Biggest explosion'
In the latest attack, Damascus was shaken by repeated explosions coming from the north-western suburbs.
Amateur video footage and eyewitness testimony suggested rocket attacks had hit weapons dumps, triggering dramatic orange-flamed blasts.
The area houses numerous military facilities, including the Jamraya research centre, designated by Syria as a scientific research centre "in charge of raising our level of resistance and self-defence".
Damascus-based journalist Alaa Ebrahim told the BBC it was "the biggest explosion" the city had seen since the conflict began two years ago.
He said residents living near Jamraya reported feeling a "mild earthquake" just before the blast, indicating that the rockets may have hit an underground facility.
Our correspondent says the Israeli attack is a high-risk strategy, and it has drawn strong reaction from the rest of the Arab world.
And the Arab League, which has given its Syria seat to the rebels, called on the UN Security Council to "act immediately" to end the attacks.
The Jamraya facility was also apparently hit in an Israeli air strike in January
Israeli officials confirmed the January strike, but insisted trucks carrying missiles to Hezbollah were the target.
After the latest attack, unnamed Western intelligence sources said the target was a weapons cache heading for Lebanon.
Israel has repeatedly said it would act if it felt advanced weapons were being transferred to militant groups in the region, especially Hezbollah
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