A previously unknown group believed to be a Syrian rebel cell said it carried out the attack.
The bombing, reminiscent of the frequent attacks during Lebanon's 1975-1990 civil war, caused enormous damage to buildings.
It set cars ablaze in Beirut's southern suburbs, a bastion of the militant group which backs Syria's embattled President Bashar al-Assad.
A military source earlier told AFP on condition of anonymity that the explosion, targeting an area between the Bir al-Abed and Rweiss neighbourhoods, was caused by a car bomb.
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"Preliminary reports say the bodies of 10 people ... Were taken to Sahel hospital, as well as 42 wounded, while four bodies... And 100 wounded were taken to Rasul al-Aazam hospital," NNA said.
The agency, quoting security sources, said another 50 wounded were taken to other hospitals.
Hezbollah's television channel showed firemen helping residents trapped in their homes escape the flames, as well as a crowd of people in panic and rage, gathered near the site of the explosion.
"Terrorism has struck the southern suburbs again," said Al-Manar's television presenter, adding that Hezbollah was "paying the price for its position".
Today's explosion came a day after Nasrallah said in an interview that his group was taking steps to ensure July's attack was not repeated.
Shortly after news of the latest attack broke, an online video surfaced showing three masked men, two of them holding rifles, in front of a white flag inscribed with the Islamic profession of faith.