The Palestinian Rehabilitation Committee raised the UNESCO flag next to the national Palestinian flag in front of Hebron's Ibrahimi Mosque or the Tomb of the Patriarchs. In a secret ballot vote 12 countries approved the inscription of Hebron's Old Town and the Cave, three objected and six abstained.
It is now divided into two sectors - one governed by the Palestinian Authority, and one by Israel, which the worldwide community considers an occupation.
And foreign ministry spokesman Emmanuel Nahshon slammed the decision as "a moral blot" which denied Jewish history in the ancient city.
A general view of the West Bank city of Hebron with the Cave of the Patriarchs, on January 18, 2017.
The Palestinian Ministry of Foreign Affairs said in a statement that Hebron's designation as a World Heritage site "transcends geography, religion, politics and ideology". Palestinians claim the West Bank is an integral part of a future independent state, a position that is widely backed internationally.
The United States has made an issue of UNESCO decisions in the past.
Israel has long accused the United Nations of inherent bias against it and there have been a number of disputes at the organisation where Palestinian president Mahmud Abbas has sought to take the battle for statehood.
The Jerusalem Center for Public Affairs, a conservative-leaning Israeli research group, said the Unesco designation ran contrary to the Palestinian commitments in the Oslo peace accords of the 1990s for the joint governance of Hebron and shared worship in the Cave of the Patriarchs.
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The UNESCO resolution, titled "Occupied Palestine" and sponsored by several Arab countries, used only the Islamic name for a sacred hilltop compound in Jerusalem.
The city is divided, in accordance with global agreements, between Palestinian and Israeli control.
The Palestinians hailed the decision.
"To disassociate Israel from the burial grounds of the patriarchs and matriarchs of our nation is an ugly display of discrimination, and an act of aggression against the Jewish people", Israel's ambassador to the UN ambassador Danny Damon said.
Subsequent to the resolution, Netanyahu called it in a Facebook posting "delusional" and said that "this time they determined that the Cave of the Machpela is Palestinian, meaning it is not Jewish".
Hebron has witnessed much Jewish-Arab strife and bloodshed.
Initial reports indicate that the Palestinian, identified as Omar Ahmad Issa, 37, was riding a motorcycle when he was struck by the Israeli auto in what appears to be a traffic accident.
Jews had been living in Hebron decades before 1967 but were forced out after violent attacks by Palestinians during the British Mandate.