It struck the Lebanese capital like an earthquake, with thousands of people left destitute and thousands more cramming into overwhelmed hospitals for treatment.
The death toll from the explosion has risen to 135, according to Lebanon's health minister.
One doctor, his own head bandaged like those of his patients, described the scene as "Armageddon".
"Wounded people bleeding out in the middle of the street, others lying on the ground in the hospital courtyard," Dr Antoine Qurban said outside Hotel Dieu Hospital in central Beirut.
As volunteers led the clear-up effort, public outrage mounted over how such a vast haul of highly combustible material - sometimes used for homemade bombs - had been stored next to a densely populated area for at least six years.
Australian in Lebanon describes terrifying moment
The government vowed to investigate and cabinet urged the military to place those responsible for storing the substance under house arrest.
But Lina Daoud, a 45-year-old resident of the devastated Mar Mikhail district where the explosion had strewn bodies in the street, blasted the country's politicians as "enemies of the state".
"They killed our dreams, our future," she said.
"Lebanon was a heaven, they have made it hell."
An initial explosion and fire at the port had sent many people to balconies and rooftops where they were filming when the fertiliser exploded, sending out a massive shockwave across the city.
In an instant, the blast left destruction likened to that caused by the country's 1975-1990 civil war, levelling buildings several hundred metres away.
City mayor Abboud said the devastation may have left 300,000 people temporarily homeless, adding to the cash-strapped country's economic misery with an estimated $3 billion in damages.
"Even in the worst years of the civil war, we didn't see so much damage over such a large area," said analyst Kamal Tarabey.
Watch the moment a huge explosion rips through Beirut
The disaster came with Lebanon already on its knees with a months-long economic crisis and currency devaluation sparking spiralling poverty even before the coronavirus pandemic hit.
The embattled government of Prime Minister Hassan Diab vowed that "those responsible for this catastrophe will pay the price".
But analyst and Georgetown University professor Faysal Itani was not optimistic.
"There is a pervasive culture of negligence, petty corruption and blame-shifting endemic to the Lebanese bureaucracy, all overseen by a political class defined by its incompetence and contempt for the public good," he said.
Messages of support poured in from around the world, including Britain's Queen Elizabeth who said she was "deeply saddened" by the disaster.
France said it would send three planes of aid, followed by a visit on Thursday by President Emmanuel Macron.
The UN's Food and Agriculture Organisation warned on Wednesday that the destruction of the port and grain silos would cause critical severe flour shortages, in a country heavily reliant on imports.
Social media user voiced outrage at the government, saying such a disaster could only strike because of the ineptitude and corruption riddling Lebanon's institutions.
Lebanese Australians feel helpless after devastation in Beirut
Hariri verdict suspended
Hospitals already stretched to the brink by a spike in coronavirus cases were pushed to new limits by the influx of wounded and were forced to turn many away.
Lebanon has recorded 5,417 cases of COVID-19, including 68 deaths.
"We've had some dark days in Lebanon over the years but this is something else," Rami Rifai, a 38-year-old engineer, said.
He spoke to AFP from a hospital where his two daughters were receiving treatment after sustaining cuts despite being half a kilometre from the seat of the blast.
"We already had the economic crisis, a government of thieves and coronavirus. I didn't think it could get worse but now I don't know if this country can get up again," he said.
Itani wrote: "Lebanon's political class should be on guard in the weeks ahead...
"But I fear that old habits die hard. These politicians are well practiced in shifting the blame. I don't expect many - if any - high-level resignations or admissions of responsibility."
In The Hague, a UN-backed tribunal said it had suspended a verdict on the 2005 murder in a huge Beirut bomb blast of former Lebanese premier Rafic Hariri, scheduled for Friday, following the latest carnage.
Readers seeking support with mental health can contact Beyond Blue on 1300 22 4636. More information is available at Beyond Blue.org.au. Embrace Multicultural Mental Health supports people from culturally and linguistically diverse backgrounds.