Israel’s strikes on Iran on Friday delivered a seismic blow to Iran’s chain of command, with Iranian officials and media reports saying that at least three of the top generals — including both the overall military commander and the leader of the powerful Islamic Revolutionary Guards Corps — had been killed.

Maj. Gen. Mohammad Bagheri, who is the chief of staff of Iran’s armed forces, was the most senior leader among the dead, according to state media. There was no immediate confirmation from the Iranian armed forces. One of General Bagheri’s deputies was also killed.

Israel has a history of successfully assassinating Iranian security officials and nuclear scientists. But it has generally picked them off one by one in covert operations as part of its long shadow war with Iran and in Lebanon or Syria.

The strikes early on Friday proved to be a stunning escalation of that tactic. Not only did they target Iran’s nuclear program and air defenses, the Israeli attacks also eliminated the top tier of military commanders all at once, targeting their residential homes, including some in secure military complexes. In some areas of the capital, Tehran, entire apartment buildings collapsed.

Gen. Hossein Salami, the commander of the Islamic Revolutionary Guards Corps, was killed in an Israeli strike within Tehran, the Revolutionary Guards said in a statement. General Salami was killed alongside a number of other members of the security body, it said.

Iran’s supreme leader, Ayatollah Ali Khamenei, who is also the commander in chief of all armed forces, said in a statement read on state television said that Israel “should anticipate a harsh punishment. The strong hand of the Islamic Republic will not let them go.” He added that a number of senior military commanders and nuclear scientists had been killed in attacks that included residential targets. “The Zionist regime with this crime has created a dark and painful fate for itself, and it will definitely receive it.” Mr. Khamenei did not mention the United States in his statement.

Iran had not been attacked by a foreign enemy with such sweeping force since 1989 when the country was at war with Iraq. Mr. Khamenei had made averting war a central part of his legacy, taking the country to the brink of conflict several times, including twice with Israel last year, but stopping short of an all-out war.

That calculation appeared to have ended on Thursday night as Iranian officials openly said the country was preparing for war. But that effort is likely to be severely hobbled by the heavy blows to Iran’s chain of command and the air defenses that protect key military, nuclear and strategic sites.

Four Iranian officials said Israel had attacked at least a dozen military bases, missile depots, nuclear and missile bases, in multiple cities in Iran including Tehran, Tabriz, Isfahan, Kermanshah and Arak. Natanz nuclear site was also severely damaged, according to state television, and the damages extended to a major highway connecting Tehran to Isfahan.

“Unfortunately they did what we did not think they would do,” said Mehdi Rahmati, a conservative political analyst in Tehran close to the government in an interview after the attacks. “Iran will be responding very seriously aiming to inflict destruction, we anticipate a period of pingpong attacks that could spread to the region.”

In addition to the military commanders, Ali Shamkhani, a senior former navy commander, and one of Iran’s most influential politicians and a close confidant of Mr. Khamenei was also killed after sustaining severe injuries in an attack on his penthouse apartment in a residential luxury tower in northern Tehran, according to three senior officials and Iranian media reports.

Mr. Shamkhani, former secretary of the Supreme National Council, was overseeing the nuclear talks with the United States as part of a committee named by Mr. Khamenei to direct the negotiations. Killing him, officials said, was targeting efforts at nuclear diplomacy.

At least three other senior Iranian figures were thought to have been killed, according to Iranian state media. They were Gen. Gholamali Rashid, a senior leader in the Iranian armed forces; Mohammad Mehdi Tehranji, an Iranian physicist; and Fereydoun Abbasi, an Iranian nuclear scientist.

As leader of the Guards force, General Salami was responsible for securing Iran’s borders and safeguarding it against any foreign attacks. The Revolutionary Guards spokesman vowed to “respond decisively and harshly to the aggression of the Zionist enemy” and deliver a decisive blow to Israel and the United States following his death.

Later, two regional sources told Reuters that at least 20 senior Iranian commanders including the head of the revolutionary guards, Aerospace Force Commander Amir Ali Hajizadeh, were killed in Israel's strikes.