Israel said the attacks followed a volley of rockets directed at Israeli positions in the Golan Heights, which caused no casualties.
The Israeli military blamed the attack on Iran's Quds Force, a special forces unit affiliated with Iran's Revolutionary Guard Corps, and said this marked the first time that Iranian forces have fired directly on Israeli troops.
Syrian and Iranian news outlets accused Israel of firing the first shot, saying it was Syria that had responded after Israel targeted the Syrian town of Quneitra with artillery fire and missiles. There was no official response from the Iranian government.
The rocket fire was followed by Israel's largest intervention in neighboring Syria in decades. Jets headed for Syria screamed over northern Israel for more than four hours, and about 70 previously identified targets were hit, according to the Israeli military.
"This was by far the largest strike we have done, but it was focused on Iranian sites," said Lt. Col. Jonathan Conricus, an Israeli military spokesman. Syrian antiaircraft batteries were also targeted after they fired on Israeli planes, he added.
In a statement carried by Syria's state news agency, an unidentified Syrian Foreign Ministry official described Israel's overnight attacks as a "new phase of aggression."
The Syrian Observatory for Human Rights, a monitoring group based in Britain, said that at least 23 people were killed in Thursday's Israeli strikes across Syria. The group said five Syrian soldiers and 18 allied militiamen died, without specifying whether any of the militiamen were Iranian. The Syrian army, however, said that only three people died in the strikes and claimed that most of the Israeli missiles were intercepted.
For residents of Damascus, it was a sleepless night. "The intensity of the blasts and their repetition was stressful," said one resident, who declined to be named for security reasons. He said that he was not fearful but that many of those close to him were. "They said that a war with Israel would be much scarier than a war with other proxies," he said.
Although the fighting raised concerns of further escalation, it remained relatively contained. Rockets fired from Syria were aimed only at targets in the occupied Golan Heights and not inside Israel's internationally recognized borders. Schools and shops in the area were open as normal Thursday, while some tourists appeared unconcerned. The altercation also did not spread to Lebanon, where Israel has fought repeated battles in recent years.
Israel and Iran have been on a collision course in Syria in recent months, as Israel has vowed not to let Iran build an expanded military presence there and has escalated attacks against Iranian targets across the border. Iran threatened retaliation after seven of its soldiers were killed by an Israeli airstrike in April.
From a viewing point on Mount Bental in the Golan Heights, Conricus pointed out where he said an Iranian rocket salvo was fired toward Israel just after midnight. Four of the 20 rockets were on target, he said, but were then intercepted, while the rest fell short.
"We saw it was very clear what the Iranians were doing, attacking Israel from Syrian soil," he said.
Israeli officials have downplayed a link between the U.S. withdrawal from the Iran nuclear deal and the immediate escalation in tensions, though Israelis in the Golan Heights were ordered to open their bomb shelters at the very moment President Donald Trump made his announcement.
Before the United States made its decision about the nuclear accord, Iran faced a "strategic uncertainty" over what would happen and did not want to take the risk of striking back, said Michael Horowitz, a senior analyst at Le Beck International, a Middle East-based geopolitical and security consulting firm. "That encouraged Tehran to be careful."
Israel, meanwhile, was looking for a chance to press its efforts at rolling back the Iranian presence in Syria, he said. "Israel was searching for an opportunity to really escalate its efforts."
An evening earlier, Israel had struck targets in Syria after detecting what Israeli officials said were suspicious military movements, reportedly killing an additional eight Iranians.
Horowitz said Israel's strategy is twofold. In part, Israel wants to delay Iranian entrenchment in Syria as much as possible and make sure it comes at the highest cost possible. At the same time, Israel is trying to back up its diplomatic efforts aimed at getting Russia and the United States to rein in Iranian expansionism.
Israeli Prime Minister Benjamin Netanyahu reiterated that point Thursday. "The international community should prevent the entrenchment of the Iranian Quds Force in Syria. We have to unite to cut off the arms of its spreading evil there and everywhere," he said, adding that Israel had responded after "Iran crossed a red line."
"The Iranian regime's deployment into Syria of offensive rocket and missile systems aimed at Israel is an unacceptable and highly dangerous development for the entire Middle East," Sanders said in a statement. "Iran's Islamic Revolutionary Guard Corps (IRGC) bears full responsibility for the consequences of its reckless actions."
The statement called on Iran and its proxies "to take no further provocative steps."
Israeli Energy Minister Yuval Steinitz, who served as intelligence minister at the time the Iran nuclear deal was negotiated and remains a member of Netanyahu's security cabinet, said that the attacks were only indirectly related to Trump's announcement.
The more direct reason for the attack, Steinitz said, was that the IRGC had deployed armed drones, ballistic missiles and short-range rockets capable of reaching Israel on Syrian soil over the past two months. "We saw that the Iranians were going beyond planning and beginning to execute their plans to start building bases and air defense systems . . . with the clear aim to be able to threaten Israel in the future," he said.
U.S. and Israeli intelligence had detected increased movement of such weaponry into Syria earlier this year, according to U.S. officials, and had anticipated such an attack launched from Syria late last month. "It didn't happen," Steinitz said, "because Israel managed to intercept and prevent or destroy some of the efforts."
He said that Israel's actions sent a "clear message" to the Iranians that Israel won't allow it "to transform Syria into an Iranian military [base] to attack Israel."
Russia, which has installed its own sophisticated air defense systems inside Syria, apparently did not activate them. Moscow's failure to become involved or even to issue a strong statement of criticism toward Israel, Steinitz said, was "a tacit message to the Iranians that Russia is not in their pocket" in Syria.
Netanyahu met with Russian President Vladimir Putin on Wednesday in Moscow, and afterward Netanyahu said he had explained that Israel had the right to defend itself against Iranian aggression.
Russian reaction to the strikes was muted Thursday. "Moscow is concerned about the growing tensions and hopes that all parties will show restraint and resort exclusively to political and diplomatic means to solve all existing problems," Kremlin spokesman Dmitry Peskov told reporters.
Foreign Minister Sergei Lavrov said that the Russians have "emphasized the need for avoiding any mutually provoking moves." Both Iran and Israel, Lavrov said, "have assured us that there are no such intentions. Nevertheless, such incidents do occur."
Russia released an analysis of the attack, saying it was carried out by 28 Israeli fighter jets firing 60 missiles and an additional 10 surface-to-surface missiles, with Syrian air defenses intercepting half of them.
Among the targets that were hit were a logistics headquarters belonging to the Quds Force, a military logistics compound in Kiswah, an Iranian military compound north of Damascus, munition storage warehouses of the Quds Force at Damascus International Airport, intelligence systems and posts associated with the Quds Force, and observation and military posts and munitions in the buffer zone between the Golan Heights and Syria proper, the Israeli army said.
Tehran's strong support for Syrian President Bashar Assad has let Iran deepen its foothold across Syria, but Iranian media downplayed Tehran's role in the violence, depicting the clashes instead as between Israel and Syria.
In the Golan Heights, where residents have become accustomed to air raid sirens due to errant fire during Syria's long civil war, things felt a little different this time.
On Thursday, the sirens sounded shortly after midnight.
"It does make you stressed," said Maayan Ben Dor, 33, a resident of Neve Ativ. "It's not Hezbollah or Hamas, it's something else."
(This story has not been edited by NDTV staff and is auto-generated from a syndicated feed.)