The Israeli military said Ibrahim Aqil, who served on Hezbollah's top military body, was the acting commander of the group's elite Radwan force and that he was killed along with about 10 other senior commanders of the unit.
One of the security sources in Lebanon said he was killed with members of the Radwan unit as they held a meeting.
The strike killed nine people and wounded 59 others, Lebanon's health ministry said, in a preliminary toll.
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The strike inflicted another blow on Hezbollah after the group suffered an unprecedented attack earlier this week in which pagers and walkie-talkies used by its members exploded, killing 37 people and wounding thousands.Â
That attack was widely believed to have been carried out by Israel, which has neither confirmed or denied its involvement.
The civil defence said its rescue teams were searching for people under the rubble of two buildings hit in Friday's strike.
The Israeli military said it had conducted a "targeted strike" in Beirut, without giving further details.
It marks the second time in less than two months that Israel has targeted a leading Hezbollah military commander in Beirut.Â
In July, an Israeli air strike 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 reported warning sirens sounded in northern Israel following the Beirut strike.Â
Israeli media reported heavy rocket fire in northern Israel.
Hezbollah said it had fired Katyusha rockets at what it described as the main intelligence headquarters in northern Israel "which is responsible for assassinations".
White House national security spokesman John Kirby said he was not aware of any Israeli notification to the US before the Beirut strike, adding that US citizens were strongly urged not to travel to Lebanon, or to leave if they are already there.
"War is not inevitable up there at the Blue Line, and we're going to continue to do everything we can to try to prevent it," said Kirby, referring to the frontier between Lebanon and Israel.
Reuters witnesses heard jet noise over Beirut around the time of the attack, and a cloud of smoke could be seen rising from the area of the strike.
"The IDF (Israel Defence Forces) conducted a targeted strike in Beirut. At this moment, there are no changes in the Home Front Command defensive guidelines," the Israeli military said.
Footage showed a badly damaged building and the street strewn with rubble and burnt out cars.
Ignited by the Gaza war, the conflict has intensified significantly this week.
On Thursday night, the Israeli military carried out its most intensive air strikes in southern Lebanon since the conflict erupted almost a year ago.
The conflict between Israel and Hezbollah is the worst since they fought a war in 2006.Â
Tens of thousands have had to leave homes on both sides of the Israel-Lebanon border.
While the conflict has largely been contained to areas at or near the frontier, this week's escalation has heightened concerns that it could widen and further intensify.
The Israeli military said army chief General Herzi Halevi met the head of the Northern Command and other division commanders on Friday morning.
Israeli newspapers reported that due to the current situation, Israeli Prime Minister Benjamin Netanyahu had delayed his trip to New York for the United Nations General Assembly next week by a day and would arrive on Wednesday.
The Iranian embassy in Lebanon said it "condemns in the strongest terms the Israeli madness that crossed all lines with targeting residential buildings in Beirut's southern suburbs".
