The country's health minister reported more than 70 people were killed and at least 3,000 others were injured.
Officials expected the number of dead to increase as emergency workers continue to search the ruins for victims. Hours after the explosion, emergency vehicles continued to transport the wounded to medical centers as army helicopters helped fight fires at the port.
The explosion was Beirut's most powerful in years. It was so huge that some people in the city thought an earthquake had occured. It could be heard and felt as far away as Cyprus, more than 200 kilometers across the Mediterranean.
The cause of the explosion has not been reported.
Abbas Ibrahim, chief of Lebanese General Security, said a supply of highly explosive material in port storage might be to blame. A local television station reported that material as ammonium nitrate.
Witnesses said an orange cloud appeared after the explosion. Such clouds often result from explosions involving nitrates.
An Israeli government official said Israel "had nothing to do" with the explosion. Israel has fought several wars in Lebanon. And tensions continue to rise between Israel and the Lebanese militant group Hezbollah.
Marwan Ramadan was about 500 meters from the port when the explosion forced him off his feet. He told the Associated Press, "It was a real horror show. I haven't seen anything like that since the days of the (civil) war."
Beirut's governor, Marwan Abboud, cried as he explored the wreckage, describing the city as "devastated."
A witness told Reuters, "I saw a fireball and smoke...People were screaming and running, bleeding. Balconies were blown off buildings."
"This country is cursed," one young man said.
The explosion happened as Lebanon's economy is facing collapse from a financial crisis and coronavirus restrictions. Many people are unemployed. Some have lost savings and others have been thrown into poverty.
I'm Caty Weaver.