As well as the damage to the old city of Syria's Aleppo and the fortress in the southeastern Turkish city of Diyarbakir, UNESCO said at least three other World Heritage sites could be affected.
"Our organization will provide assistance within its mandate," said UNESCO director general Audrey Azoulay.
A statement from UNESCO said it was "particularly concerned" about the old city of Aleppo, which has been on its list of World Heritage in Danger since 2013 due to the Syrian civil war.
"Significant damage has been noted in the citadel. The western tower of the old city wall has collapsed and several buildings in the souks have been weakened," it said.
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 by government forces left it disfigured.
Syria's directorate of antiquities had already raised concern about the damage on Wednesday, saying parts of Aleppo's northern defensive walls had collapsed.
In Turkey, UNESCO said it was saddened by the "collapse of several buildings" at the World Heritage site of the Diyarbakir Fortress and the adjacent Hevsel Gardens.
It emphasized that the entire area was an important center of the Roman, Sassanid, Byzantine, Islamic and Ottoman periods.
The pre-dawn quake hit near Gaziantep in southeastern Turkey at a depth of about 18 kilometers, the US Geological Survey said.
With weather conditions and the remote nature of the areas making access and information hard to come by, UNESCO said other sites on the World Heritage list not far from the epicenter could be affected.
It said these included the famed neolithic site of Gobekli Tepe in Sanliurfa province, home to the world's oldest known megaliths some 10,000 years old.
UNESCO is also concerned about the Nemrut Dag site, one of Turkey's most iconic attractions due to the giant statues that are part of an ancient royal tomb erected high on a mountain, it said.
The third site is the neo-Hittite archaeological site of Arslantepe outside Malatya, a city also badly hit by the earthquake.
"UNESCO is mobilizing its experts, to establish a precise inventory of the damage with the aim of rapidly securing and stabilizing these sites," it said.
