The blast has been linked to a large supply of confiscated and potentially unsecured explosive material, stored in a warehouse at the city's port, close to populated areas. As world leaders and international organizations step in to offer assistance, local officials are also launching an investigation into the blast.
As day breaks in Lebanon, authorities are scrambling to treat the wounded, search for survivors, and assess the full extent of the damage. Here's what we know so far.
The basics: What, where, when
The explosion took place at 6:07 p.m. local time near Beirut's port and central district, close to many highly-populated areas and tourist sites.
Nearby landmarks include the historic Martyrs' Square; the Gemmayzeh and Mar Mikhael neighborhoods, fixtures of the Beirut bar scene; the landmark Mohammad Al-Amin Mosque; Grand Serail, the government palace; and Baabda Palace, the official residence of the Lebanese President.
The explosion tore through the city, flipping cars, shattering glass and causing some homes to crumble. Damaged buildings include the headquarters of former Prime Minister Saad Hariri and CNN's bureau in downtown Beirut. Homes as far as 10 kilometers (6 miles) away were damaged, according to witnesses.
The blast was even felt in Cyprus, around 240 kilometers (150 miles) away, and registered as a 3.3 magnitude earthquake.
What are the casualties?
At least 80 people were killed in the blast and at least 4,000 wounded, Health Minister Hamad Hassan said in a phone interview Wednesday morning with one of Lebanon's national television channels. This figure is expected to rise, he said.
"There are many people missing until now. People are asking the emergency department about their loved ones and it is difficult to search at night because there is no electricity. We are facing a real catastrophe and need time to assess the extent of damages," Hasan said in a Reuters report.
Among the dead are the secretary-general of the Kataeb political party, Nazar Najarian, according to Lebanon state-run NNA news. He was in his office when the explosion happened, and died after being critically injured.
At least 10 firefighters working for Beirut's municipality are missing, said the city's governor Marwan Abboud.
At least one Australian was killed, and the Australian Embassy building has been "significantly compromised," said Australian Prime Minister Scott Morrison.
One Japanese citizen and one Indonesian national were also injured, according to authorities from the two countries.
Some naval peacekeepers with the United Nations Interim Force in Lebanon (UNIFIL) have also been injured, some seriously. They have been transported to hospital for treatment, said UNIFIL.
What caused the blast?
In the immediate aftermath, there were conflicting reports, and it was initially blamed on a major fire at a warehouse for firecrackers near the port.
United States President Donald Trump added to the confusion when he