Referring to reports that thousands of books on philosophy, law, science and poetry have been torched in recent weeks, UNESCO Director-General Irina Bokova said it was part of a campaign of "cultural cleansing."
"If confirmed, this would be one of the most devastating acts of destruction of library collections in human history," UNESCO said.
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"Such destruction is a cruel reminder that the nations of the world must remain united to combat such fanaticism today," Bokova added.
Islamic State extremists currently hold the city of Mosul, the second-largest city in Iraq.
US air strikes against the group have aimed to put pressure on the group. Kurdish peshmerga forces have also launched successful offensives against IS-held roads near Mosul.
UNESCO said the "armed extremists in Iraq" were targeting "cultural heritage, cultural and religious minorities, and the documents and written evidence of one of the oldest civilisations in human history."