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 referred to the incident at an "attack," though US Defense Department officials told CNN afterward there was no indication that was the case. Lebanese officials also raised concerns with US diplomats about the use of the phrase "attack," two State Department officials said.
Later, in the early hours of Wednesday morning, Prime Minister Hassan Diab said that about 2,750 metric tons of ammonium nitrate, a highly explosive material, had been stored at a port warehouse for the past six years "without preventive measures."
Lebanon's general security chief said a "highly explosive material" had been confiscated years earlier and stored in the warehouse, which is just a few minutes' walk from Beirut's shopping and nightlife districts.
Officials have so far not commented on what might have ignited the blaze.
Diab announced an investigation into the explosion, saying the probe would include "revelations that will be announced about this dangerous warehouse which has been present since 2014."
"I will not rest until we find those responsible for what happened, hold them accountable, and impose maximum punishment," he said in a statement, saying it was "unacceptable" that so much ammonium nitrate had been stored "while endangering the safety of citizens."
However, experts have cautioned that the blast could have been caused by more than just ammonium nitrate.
Anthony May, a retired ATF explosives investigator for the US government, said the color of the cloud after the blast suggests there may have been other compounds involved. And Robert Baer, a former CIA operative with extensive experience in the Middle East, said "that orange ball (of fire)" indicated possible military explosives.
"This is not just ammonium nitrate," Baer said.
What is ammonium nitrate?
Ammonium nitrate, a compound of ammonia and nitrogen, is a highly volatile material used in agricultural fertilizers and bombs.
One of the worst disasters in US history involving a form of ammonia occurred in April 1947 when a ship loaded with ammonium nitrate caught fire while docked in Texas City. The fire caused an explosion and additional fires that damaged more than 1,000 buildings and killed nearly 400 people, according to the website of the Texas Historical Association.
For perspective, that explosion was triggered by 2,300 US tons (about 2087 metric tons) of ammonium nitrate, according to US Homeland Security.
And the 1995 Oklahoma City Bombing, a US domestic terror attack that killed 169 people and injured 467, used only two US tons (1.8 metric tons) of ammonium nitrate.
What are the ongoing response efforts?
In the hours following the bombing, authorities and humanitarian organizations launched search and rescue efforts. The Lebanese President has directed all armed forces to respond to the disaster, and to patrol affected areas for additional security.
Aid groups like UNICEF and the Red Cross have teams on the ground assisting authorities, and have put out urgent open calls for blood donations.
Hospitals were quickly inundated, with doctors conducting triage as dozens flooded into emergency rooms. The emergency section of one major hospital, the American University of Beirut Medical Center, became unable to receive more patients. Four hospitals are out of service after sustaining damage in the explosion, said the health minister.
Other countries and international organizations quickly stepped in to help, and the United Nations and World Health Organization are working with Lebanese authorities.
President Trump, Australian Prime Minister Morrison and Russian President Vladimir Putin all offered support and assistance. French President Emmanuel Macron said "rescue and aid" were on the way to Lebanon, and Israel has formally extended humanitarian medical assistance.
The spokesman for Egypt's Ministry of Foreign Affairs said the Egyptian field hospital in Beirut was ready to provide assistance, and that it had already received a number of patients.
Middle Eastern neighbors including Qatar, Kuwait and Iraq will also send field hospitals, medical supplies and oil to Lebanon, state-run Lebanese NNA said.
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