Israel's raids came after it intercepted what it said was an Iranian drone entering its airspace from Syria.
It marked the first time Israel publicly acknowledged attacking what it identified as Iranian targets in Syria since the war began.
The Israeli military issued a warning to Tehran, saying it was responsible for the drone that entered Israel, which it labelled an "attack."
It said its reprisals after the exchange were "large- scale" raids.
"A few minutes ago, (Israeli aircraft)... targeted the Syrian Aerial Defence System and Iranian targets in Syria," a military statement said.
"Twelve targets, including three aerial defence batteries and four Iranian targets that are part of Iran's military establishment in Syria were attacked."
Israel has repeatedly warned in recent weeks against the presence of Iranian forces in neighbouring Syria.
The Israeli pilots of the crashed F16 were reported alive, although one was severely wounded.
According to the Israeli military, the confrontation began with a drone entering its airspace.
Israeli forces identified an "Iranian UAV (unmanned aerial vehicle)" launched from Syria and intercepted it in Israeli airspace with a combat helicopter, a statement said.
"Massive Syrian anti-air fire, one F16 crashed in Israel, pilots safe."
Police said the F16 crashed in the Jezreel valley in northern Israel.
It was not clear if the jet crashed as a direct result of the Syrian fire.
According to a separate military statement, "multiple anti-aircraft missiles were fired at IAF (Israel Air Force) aircraft."
"The pilots of one of the aircraft abandoned as per procedure. The pilots landed in Israeli territory and were taken to the hospital for medical treatment."
Conricus said the army had confirmed "accurate hits of (the) Iranian UAV control facility" in Syria.
"Iran is responsible for this severe violation of Israeli sovereignty," Conricus said on Twitter.
Syria said its air defences repelled two Israeli raids on its military bases in the centre of the country, hitting more than one warplane during the first.
"Our air defences repelled it and hit more than one plane."
The Syrian Observatory for Human Rights, a Britain- based monitor of the seven-year civil war, said the Israeli raids had targeted several military bases in the east of the central province of Homs.
It said the bases are used by both Iranian and Russian military personnel deployed in support of the regime.
Air raid sirens had gone off in Israel in the early hours of the morning following the UAV interception and raids.
The army said it was "monitoring events and is fully prepared for further action, depending on assessments and necessity."
Israeli Prime Minister Benjamin Netanyahu has held a series of meetings in recent months with Russian President Vladimir Putin on Iran's influence in war-torn Syria and Lebanon.
Netanyahu has been seeking to persuade Russia to limit Iran's presence near Israeli territory and to stop it from entrenching itself militarily in Syria.
In a meeting in Moscow last month, Netanyahu reiterated Israel's concerns of what he described as the attempts of Iran to establish a military presence in Syria and produce accurate weapons against Israel there.
"We won't accept either of those, and will act according to our needs," Netanyahu said following the meeting with Putin.
Israel remain technically at war with Syria and occupies a swathe of the strategic Golan Heights that it seized in the Six-Day War of 1967 and later annexed in a move never recognised by the international community.
On Tuesday, Netanyahu took members of his security cabinet for a tour of the Israeli-occupied side, where they were briefed by the military on the situation.
"We want peace, but are prepared for any scenario, and suggest that nobody tries us," he said.
Israel has sought to avoid direct involvement in the Syrian war, but acknowledges carrying out dozens of air strikes there to stop what it says are advanced arms deliveries to Hezbollah.
(This story has not been edited by Business Standard staff and is auto-generated from a syndicated feed.)