Local officials in Turkey put the initial death toll at 53, although it threatened to climb substantially higher because it caught most people while they were still at home asleep.
At least 42 people also died in government-controlled parts of northern Syria, state media said.
Television images showed shocked people in Turkey standing in the snow in their pyjamas, watching rescuers dig through the debris of damaged homes.
The quake struck at 04:17 am local time (0117 GMT) at a depth of about 17.9 kilometres (11 miles), the US agency said, with a 6.7-magnitude aftershock striking 15 minutes later.
Turkey’s AFAD emergencies service centre put the first quake’s magnitude at 7.4.
The earthquake was one of the most powerful to hit the region in at least a century.
“I convey my best wishes to all our citizens who were affected by the earthquake,” Turkish President Recep Tayyip Erdogan tweeted.
“We hope that we will get through this disaster together as soon as possible and with the least damage.”
The earthquake levelled dozens of buildings across major cities of southern Turkey as well as neighbouring Syria, a country gripped by more than a decade of violence that has killed hundreds of thousands and displaced millions of people.
Prayers for Turkey , Syria , Lebanon and Jordan pic.twitter.com/3zbD57avCk
— MNA (@Engr_Naveed111) February 6, 2023
Images on Turkish television and social media showed rescuers digging through the rubble of levelled buildings in the city of Kahramanmaras and neighbouring Gaziantep.
A fire lit up the night sky in one image from Kahramanmaras, although its origin remained unclear.
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NTV television said buildings also crumbled in the cities of Adiyaman, Malatya and Diyarbakir.
CNN Turk television said the quake was also felt across parts of central Turkey and the capital Ankara.
Syrian state television reported that a building near Latakia, on the west coast of Syria, had collapsed.
Pro-government media said several buildings had partially collapsed in Hama, central Syria, with civil defence and firefighters working to pull survivors out of the rubble.
Raed Ahmed, who heads Syria’s National Earthquake Centre, told pro-government radio that this was “historically, the biggest earthquake recorded in the history of the centre”.
Naci Gorur, an earthquake expert with Turkey’s Academy of Sciences, urged local officials to immediately check the region’s dams for cracks to avert potentially catastrophic floodings.
Turkey is in one of the world’s most active earthquake zones
The Turkish region of Duzce suffered a 7.4-magnitude earthquake in 1999 — the worst to hit Turkey in decades.
Prayers for Turkey, Syria, Lebanon and all the other places affected by the colossal quake today. #Turkey #earthquake pic.twitter.com/LWp5UbhnLN
— Amina Zubair (@amnakhani123) February 6, 2023
That quake killed more than 17,000 people, including about 1,000 in Istanbul.
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Experts have long warned a large quake could devastate Istanbul, which has allowed widespread building without safety precautions.
A magnitude-6.8 quake hit Elazig in January 2020, killing more than 40 people.
And in October that year, a magnitude-7.0 quake hit Turkey’s Aegean coast, killing 114 people and wounding more than 1,000.