The blast sent shock waves across the city and was heard as far away as Cyprus, some 150 miles to the north west, with many there initially believing it to be an earthquake.
It comes at a critical moment for Lebanon, with the country already struggling to cope with the twin challenges of financial collapse and a surge in coronavirus infections.
So what caused the fatal disaster? And how many lives have been affected? Here is everything we know so far:
The blast was sparked after flames broke out at a port warehouse storing highly explosive material, at about 4pm UK time on August 4.
Lebanon’s president Michel Aoun said that 2,750 tonnes of ammonium nitrate, used in fertilisers and bombs, had been stored for six years at the port without proper safety measures in place.
The country’s prime minister Hassan Diab said the warehouse had been the subject of warnings dating as far back as 2014.
He said the Government would “reveal facts” about the site but did not want to pre-empt an investigation.
Officials did not say what caused the blaze that set off the blast.
But security sources and local media said it was started by welding work being carried out on a hole in the warehouse.
How many people died in the incident?
At least 100 people were killed and more than 4,000 injured. However, the tolls are expected to rise.
Rodney Eid, of Red Cross Lebanon, told BBC Radio 4’s Today programme this morning: “The preliminary report indicates around 4,000 people have been injured and at least 100 have lost their lives.
“Our teams are still searching the area, and it is a big area, around the blast – to look for survivors, to look for people who are injured.
“We have also set up two triage and first aid locations next to the blast area so that minor injuries can be treated there as we were overwhelmed with the number of calls yesterday.
“We were trying to respond to the most vulnerable and to the critical cases first.”
He added that “there are a lot of people who are missing”.
“I expect the death toll to rise,” he said.
Footage from the scene showed entire streets in ruins, with people trapped beneath the rubble.
What’s the international response been?
Boris Johnson has confirmed that British nationals were among those caught up in the blast.
The Prime Minister said the Government is “ready to provide support in any way we can”, and Foreign Secretary Dominic Raab said the UK stands in solidarity with Lebanon.
In a tweet, Mr Johnson said: “The pictures and videos from Beirut tonight are shocking. All of my thoughts and prayers are with those caught up in this terrible incident.
“The UK is ready to provide support in any way we can, including to those British nationals affected.”
The pictures and videos from Beirut tonight are shocking. All of my thoughts and prayers are with those caught up in this terrible incident. The UK is ready to provide support in any way we can, including to those British nationals affected.— Boris Johnson (@BorisJohnson)August 4, 2020
All staff at the British embassy in Beirut are accounted for, but some have sustained “non-life-threatening injuries”.
A spokesman for the Foreign Office said: “All Embassy staff are accounted for. A small number have sustained non-life-threatening injuries and where necessary are receiving medical attention.”
“It would seem like it based on the explosion,” Mr Trump told reporters in Washington.
Later, two unnamed US officials contradicted the president, saying it was unclear where he was receiving his information from but that initial information didn’t suggest the explosion was an attack.
What happens next?
Lebanon’s Supreme Defence Council has recommended declaring a two-week state of emergency in Beirut and handing over security responsibilities to military authorities.
President Aoun also announced that the government is to release 100 billion lira (£50.5 million) of emergency funds from the country’s 2020 budget.
The head of Lebanon's Red Cross, George Kettani, said the charity was coordinating with the country’s health ministry to set up morgues because hospitals were overwhelmed.
The country will observe an official period of mourning for three days from today.