"It is another delusional decision by UNESCO," Netanyahu said in Hebrew, in a video posted online.
"This time they ruled the Tomb of the Patriarchs is a Palestinian site, meaning not a Jewish site, and it is in danger."
A committee of the UN's cultural arm voted 12 to three -- with six abstentions -- to give heritage status to Hebron's Old City in the occupied West Bank, which is home to more than 200,000 Palestinians and a few hundred Israeli settlers.
The site is holy to both religions, with Old Testament figures including Abraham believed to be buried there.
The Palestinians hailed the vote as a diplomatic victory.
It is the latest UNESCO decision to anger Netanyahu, following a resolution on Jerusalem in May which strongly criticised the Jewish state's occupation of the eastern part of the city.
Netanyahu said at the time the "absurd" vote denied the Jewish connection to the city.
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