Dozens of nations pledged aid after the 7.8-magnitude quake, which hit as people were still sleeping and amid freezing weather that has hampered emergency efforts.
Multi-storey apartment buildings full of residents were among the 5,606 structures reduced to rubble in Turkey, while Syria announced dozens of collapses, as well as damage to archaeological sites in Aleppo.
"That was the first time we have ever experienced anything like that," said Melisa Salman, a 23-year-old reporter in the southeastern Turkish city of Kahramanmaras.
"We thought it was the apocalypse."
The head of Syria's National Earthquake Centre, Raed Ahmed, called it "the biggest earthquake recorded in the history of the centre".
The initial quake was followed by dozens of aftershocks, including a 7.5-magnitude tremor that jolted the region in the middle of search and rescue work on Monday.
"We managed to save three people, but two were dead," said Halis Aktemur, 35, in Turkey's southeastern city of Diyarbakir after the quake that was felt as far away as Greenland.
In the southeastern Turkish city of Sanliurfa, rescuers were working into the night to try and pull survivors from the wreckage of a seven-storey building that had collapsed.
"There is a family I know under the rubble," said 20-year-old Syrian student Omer El Cuneyd.
"Until 11:00 am or noon, my friend was still answering the phone. But she no longer answers. She is down there."
Despite temperatures falling below zero, frightened residents in the city were preparing to spend the night on the streets, huddling around fires for warmth.
Nearby, Mustafa Koyuncu was sitting packed inside his stationary car with his wife and their five children, scared to move.
"We are waiting here because we can't go home," the 55-year-old told AFP. "Everyone is afraid."
- 'Apocalypse' -
At least 1,444 people died Monday across Syria, the government and rescuers said.
The new toll brings the total deaths in both countries to at least 3,823 after Turkey revised its toll earlier to 2,379.
Nearly 14,500 people were injured and 4,900 buildings flattened, Ankara announced late Monday.
Turkey declared seven days of mourning for the dead.
The rescue was being hampered by a winter blizzard that covered major roads in ice and snow. Officials said the quake made three major airports in the area inoperable, further complicating deliveries of vital aid.
Monday's first earthquake struck at 4:17am (0117 GMT) at a depth of about 18 kilometres (11 miles) near the Turkish city of Gaziantep, which is home to around two million people, the US Geological Survey said.
Denmark's geological institute said tremors reached the east coast of Greenland about eight minutes after the main quake struck Turkey.
More than 12,000 people are injured in Turkey, the disaster management agency said, while Syria said at least 3,411 people were injured.
- 'People under debris' -
Osama Abdel Hamid, a quake survivor in Syria, said his family was sleeping when the shaking began.
"The walls collapsed over us, but my son was able to get out," he said.
"He started screaming and people gathered around, knowing there were survivors, and they pulled us out from under the rubble."
The United States, the European Union and Russia all immediately sent condolences and offers of help.
Ukrainian President Volodymyr Zelensky offered to provide "the necessary assistance" to Turkey, whose combat drones are helping Kyiv fight the Russian invasion.
Images on Turkish television showed rescuers digging through rubble across neighbourhoods of almost all the big cities running along the border with Syria.
Some of the heaviest devastation occurred near the quake's epicentre between Kahramanmaras and Gaziantep, where entire city blocks lay in ruins under gathering snow.
A famous mosque dating back to the 13th century partially collapsed in the province of Maltaya, along with a 14-story building with 28 apartments that housed 92 people.
The UN cultural agency UNESCO expressed fears over heavy damage in two cities on its heritage list -- Aleppo in Syria and Diyarbakir in Turkey.
Aleppo was Syria's pre-war commercial hub and considered one of the world's longest continuously inhabited cities, boasting markets, mosques, caravanserais, and public baths, but a brutal siege imposed on rebels left it disfigured.
- Power outages -
The Syrian health ministry reported damage across the provinces of Aleppo, Latakia, Hama and Tartus, where Russia is leasing a naval facility.
AFP correspondents in northern Syria said terrified residents ran out of their homes after the ground shook.
Even before the tragedy, buildings in Aleppo -- Syria's pre-war commercial hub -- often collapsed due to the dilapidated infrastructure, which has suffered from lack of war-time oversight.
Officials cut off natural gas and power supplies across the region as a precaution, also closing schools for two weeks.
Turkey is in one of the world's most active earthquake zones.
The country's last 7.8-magnitude tremor was in 1939, when 33,000 died in the eastern Erzincan province.
The Turkish region of Duzce suffered a 7.4-magnitude earthquake in 1999, when more than 17,000 people died.
Experts have long warned a large quake could devastate Istanbul, a megalopolis of 16 million people filled with rickety homes.
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