The 7.8 magnitude earthquake struck before dawn near the Turkish city of Gaziantep, about 40 kilometres from the Syrian border.
It left northwestern Syria "in a state of catastrophe" with "destruction, devastation, and collapse of buildings," the White Helmets rescue group said on Twitter.
"Hundreds of injuries, dozens of deaths, many trapped under the rubble or stranded in the winter cold," the group which operates in rebel-held parts of the war-torn country said, without providing a specific number.
A doctor at a hospital in the countryside of the northwestern province of Idlib said it had received the bodies of 30 people.
"After the earthquake which occurred today, we received 100 injured and 30 martyrs," said Doctor Majid Ibrahim of the Al-Rahma hospital.
"The situation is too bad because a lot of people are still under the debris of the buildings," he told AFP.
Earlier, a medical official said at least eight people were killed in Azaz and Al-Bab, regions of northern Syria controlled by pro-Turkish rebels.
In government-controlled parts of war-torn Syria, the death toll from the earthquake was at least 237, according to the health ministry.
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