The Israeli military and a security source in Lebanon said Ibrahim Aqil had been killed along with other senior members of an elite Hezbollah unit in the air strike, sharply escalating the year-long conflict between Israel and the militant group.
Lebanon's health ministry said at least 14 people died and the toll was expected to climb as rescue teams worked through the night.
It was not immediately known whether the toll included Aqil and the other senior Hezbollah commanders.
Earlier, the military said at least 66 people were injured, nine of whom were in critical condition.
A second security source said the attack was carried out with multiple missiles that blasted into the opening of a building's garage.
The explosion tore into the building's lower levels as Akil met other top commanders inside.
Our enemies have no place of refuge - not even the Dahieh in Beirut. — יואב גלנט - Yoav Gallant (@yoavgallant) We will continue operating against Hezbollah until we achieve our mission: ensuring the safe return of Israel's northern communities to their homes.September 20, 2024
Witnesses reported hearing a loud whistling and several consecutive blasts at the time of the strike.
In a brief statement carried by Israeli media, Prime Minister Benjamin Netanyahu said Israel's goals were clear and its actions spoke for themselves.
Defence Minister Yoav Gallant, who has said this week that Israel is launching a new phase of war on the northern border, posted on X: "The sequence of actions in the new phase will continue until our goal is achieved: the safe return of the residents of the north to their homes."
Hezbollah made no statement on the Israeli strike or Aqil's fate.
Its media office issued two statements on Friday night saying the group had fired rockets at two Israeli positions at 8.40pm, hours after the Israeli attack.
Tens of thousands of people have fled from homes on both sides of the Israel-Lebanon border since Hezbollah began rocketing Israel in what it says is sympathy with the Palestinians in parallel to the war in the Gaza Strip.
Israel, which last fought an all-out war against Hezbollah 18 years ago, has said it will use force if necessary to ensure its citizens can return.
The Israeli military described Aqil as the acting commander of the Radwan special forces unit, and said it had killed him along with about 10 other senior commanders as they met.
Aqil sat on Hezbollah's top military council, sources in Lebanon told Reuters.
The strike inflicted another blow on Hezbollah after two days of attacks on the group in which pagers and walkie-talkies used by its members exploded, killing 37 people and wounding thousands.
Those attacks were widely believed to have been carried out by Israel, which has neither confirmed or denied its involvement.
Local broadcasters showed groups of people gathered near the site, and reported they were searching for people who had been in the vicinity and were still missing, most of them children.
Drones were still flying over Beirut's southern suburb hours after the strike.
"We are not afraid but we want a solution. We cannot continue with the country like this," said Alain Feghali, a resident of Beirut who spoke to Reuters.
"War? I don't know if it started or not but nothing is reassuring. It is clear that the two sides will not stop."
The United Nations Special Coordinator for Lebanon Jeanine-Hennis Plasschaert said Friday's strike in a densely populated area of Beirut's southern suburbs was part of "an extremely dangerous cycle of violence with devastating consequences. This must stop now."
The strike marked the second time in less than two months that Israel has targeted a leading Hezbollah military commander in Beirut.
In July, an Israeli airstrike killed Fuad Shukr, the group's top military commander.
Aqil has a $US7 million ($A10 million) bounty on his head from the United States over his link to the deadly bombing of Marines in Lebanon in 1983, according to the US State Department website.
The Israeli military said Aqil had been head of Hezbollah operations since 2004 and was responsible for a plan to launch a raid on northern Israel, similar to the Hamas-led attack on southern Israel on October 7 that triggered the war in Gaza.
"The Hezbollah commanders we eliminated today had been planning their 'October 7th' on the northern border for years," Israeli army chief General Herzi Halevi said.
"We reached them, and we will reach anyone who threatens the security of Israel's citizens."
