The strike occurred overnight Thursday into Friday, the officials said.
It didn't appear that a chemical weapons site was targeted, they said, and one official said the strike appeared to have hit a warehouse.
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The US officials spoke on condition of anonymity because they were not authorised to discuss the matter publicly.
Israel has targeted weapons in the past that it believes are being delivered to the Lebanon-based militant group Hezbollah.
Earlier this week, Hezbollah leader Sheikh Hassan Nasrallah said his group would assist Syrian President Bashar Assad if needed in the effort to put down a 2-year-old uprising.
Israeli Embassy spokesman Aaron Sagui would not comment on Friday night specifically on the report of an Israeli strike into Syria.
In 2007, Israeli jets bombed a suspected nuclear reactor site along the Euphrates River in northeastern Syria, an attack that embarrassed and jolted the Assad regime and led to a buildup of the Syrian air defence system.
Russia provided the hardware for the defence systems upgrade and continues to be a reliable supplier of military equipment to the Assad regime.
Word of the new strike, first reported by CNN, came hours before President Barack Obama told reporters at a news conference in Costa Rica on Friday that he didn't foresee a scenario in which the US would send troops to Syria.
More than 70,000 peoples have died and hundreds of thousands have fled the country as the Assad regime has battled rebels.
The Israeli strike also follows days of renewed concerns that
Syria might be using chemical weapons against opposition forces.
Obama has characterised evidence of the use of chemical weapons as a "game-changer" that would have "enormous consequences".
"I do not foresee a scenario in which boots on the ground in Syria, American boots on the ground in Syria, would not only be good for America but also would be good for Syria."
Obama said there was evidence that chemical weapons had been used in Syria, but that "we don't know when, where or how they were used".
But if "strong evidence" is found of such weapons being used by the regime of President Bashar al-Assad, "then that is a game changer for us" because "there is a possibility that it lands in the hands of organisations like Hezbollah".
