Officials say they expect the death toll to rise after Tuesday's blast as emergency workers dig through rubble to rescue people and remove the dead.

It was the most powerful explosion in years to hit Beirut, which is already reeling from economic crisis and a surge in coronavirus infections.

Lebanon's interior minister said initial information indicated highly explosive material, seized years ago and stored at the port, had blown up.

Israel, which has fought several wars with Lebanon, has denied any role and offered help.

"What we are witnessing is a huge catastrophe," the head of Lebanon's Red Cross George Kettani told broadcaster Mayadeen.

"There are victims and casualties everywhere."

Hours after the blast, which erupted shortly after 6 pm local time, a fire still blazed in the port district, casting an orange glow across the night sky as helicopters hovered and ambulance sirens sounded across the capital.

A security source said victims were taken for treatment outside the city because Beirut hospitals were packed with wounded.

Ambulances from the north and south of the country and the Bekaa valley to the east were called in to help.

The blast was so big some residents in the city, where memories of heavy shelling during the 1975 to 1990 civil war live on, thought an earthquake had struck.

Dazed, weeping and wounded people walked through streets searching for relatives.

"I promise you that this catastrophe will not pass without accountability," Prime Minister Hassan Diab told the nation.

"Those responsible will pay the price," he said in his televised address, adding that details about the "dangerous warehouse" would be made public.

The interior minister told Al Jadeed TV that ammonium nitrate had been stored at the port since 2014.

The US embassy in Beirut warned residents in the city about reports of toxic gases released by the blast, urging people to stay indoors and wear masks if available.

Footage of the explosion shared by residents on social media showed a column of smoke rising from the port followed by an enormous blast, sending up a white cloud and a fireball into the sky.

Those filming the incident from high buildings two kilometres from the port were thrown backwards by the shock.

It was not immediately clear what caused the initial blaze on Tuesday that set off the blast.

Lebanon's health minister said more than 50 people had been killed and more than 2750 injured. Lebanon's Red Cross said hundreds of people had been taken to hospitals.

The governor of Beirut port told Sky News a team of firefighters, who were battling the initial blaze, had "disappeared" after the explosion.

President Michel Aoun called for an emergency cabinet meeting on Wednesday and said a two-week state of emergency should be declared. He said it was "unacceptable" that 2750 tonnes of ammonium nitrate were stored for six years without safety measures.

The prime minister called for a day of mourning.

The explosion occurred three days before a UN-backed court is due to deliver a verdict in the trial of four suspects from the Shi'ite Muslim group Hezbollah over a 2005 bombing which killed former Prime Minister Rafik al-Hariri and 21 others.

Hariri was killed by a huge truck bomb on the same waterfront.

Australian Associated Press