It is not yet clear what caused the explosion in the city's port region. Video posted online showed a large mushroom cloud and destroyed buildings.
Hospitals are said to be overwhelmed by casualties.
Lebanon's internal security chief said the blast happened in an area housing highly explosive materials.
The explosion comes at a sensitive time for Lebanon, with an economic crisis reigniting old divisions. Tensions are also high ahead of Friday's verdict in a trial over the killing of ex-Prime Minister Rafik Hariri in 2005.
Lebanese Health Minister Hamad Hasan has spoken of many injuries and extensive damage, and the Lebanese Red Cross says hundreds of people have been taken to hospital.
A BBC journalist at the scene reported dead bodies and severe damage - enough to put the port out of action.
Reuters news agency quotes sources as saying 10 bodies have been pulled from the wreckage.
The cause of the explosion is still not known, but some reports suggest it may have been an accident. Lebanon's National News Agency reported a fire breaking out at what it called an explosives depot at the port before the explosion.
A large building in the port, which is close to the city centre, was blown apart.
Local media showed people trapped beneath rubble. A witness described the first explosion as deafening. Video footage showed wrecked cars and blast-damaged buildings.
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