The Syrian Observatory for Human Rights reported that the attack targeted "Iranian forces and pro-Assad militias" and that "there are likely fatalities".
An Israeli military spokeswoman declined to comment on the latest incident.
Attacks on the T-4 based mark a new phase in Israel's defense against Iranian provocation, which has included in the past sending an armed drone into Israeli airspace.
Israel usually does not claim the strikes, but has long said it will not allow Iran to establish a military presence in Syria. Israel's air force has struck scores of targets it described as Iranian deployments or arms transfers to Iran-backed Hezbollah. Successful Israeli attacks on Syrian bases, however, routinely happen without Israel responding publicly.
"At the meeting I will reiterate the two basic principles of Israel's policy: First, we will not tolerate the establishment of a military presence by Iran and its proxies anywhere in Syria, not close to the border and not far away from it".
Iran executes eight over deadly IS attacks Iran's paramilitary Revolutionary Guard responded to the attack by launching six missiles into eastern Syria, targeting ISIL. A total of 22 people - 17 civilians and 5 assailants - were killed during the attacks.
Meanwhile, the TV said six missiles landed in the vicinity of the base during the airstrike on Sunday, adding that damages were caused with no reports on casualties yet.
The attack comes amid a Syrian government offensive against insurgent groups near the Israeli-occupied Golan Heights.
Israel then carried out what it called "large-scale" raids on Syrian air defence systems and Iranian targets, which reportedly included T4.
Israel seized a large swathe of the Golan Heights from Syria in the 1967 Six-Day War and later annexed it in 1981, in a move never recognised by the global community.
In February, Israeli fighter jets hit Iranian command units stationed at the base after an Iranian unmanned aircraft violated Israeli airspace. "Second, we will demand that Syria, and the Syrian military, strictly uphold the 1974 Separation of Forces Agreement", Netanyahu said.