"Preliminary information indicates that there was highly explosive material that was confiscated a while back and stored", Interior Minister Mahdmoud Fehme told a local television station.
The explosion came as a United Nations -backed court is trying four people from the Shi'ite Hezbollah group suspected of killing Lebanon's former Sunni leader Rafik Hariri in a truck bombing 15 years ago, causing regional upheaval.
The blasts were heard as far away as Nicosia on the eastern Mediterranean island of Cyprus, 240 kilometres (150 miles) away.
Lebanese Armenian politician, Secretary General of Lebanon's Christian Kataeb Party, or Phalange, Nazar Najarian has been killed in a powerful explosion in Beirut, Russia Today reports.
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An Israeli official said Israel had nothing to do with the blast.
Outside the Clemenceau Medical Centre, dozens of wounded people, many covered in blood, were rushing to be admitted to the centre, including children. There were hundreds of casualties, with bodies buried under the rubble, officials said.
Some reports said there might have been a second blast Tuesday across the city near the Hariri family residence.
The outlet reported on "unconfirmed reports" of a second blast, and points out that "A United Nations tribunal is due to issue its verdict in the trial of four suspects in the murder by vehicle bomb of [Lebanon ex-PM Rafic Baha El Deen Al ] Hariri".
The explosion comes as Lebanon experiences its worst economic and financial crisis in decades.
The huge blast sent a mushroom cloud over Beirut.
A woman close to the scene told the AFP correspondent that it "felt like an earthquake", and added that the two explosions today "felt bigger than the explosion in the assassination of Rafic Hariri in 2005".