"I am extremely concerned for the safety of up to 1.5 million people living in Mosul who may be impacted by military operations to retake the city from ISIL," Stephen O'Brien said, referring to the Islamic State jihadist group.
He warned that "families are at extreme risk of being caught in cross-fire or targeted by snipers."
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With the support of Iran and a US-led coalition, Iraqi forces have since regained much of the ground lost to IS. Mosul is the extremist group's last major stronghold in Iraq.
Iraqi Prime Minister Haider al-Abadi has said only government forces will enter Mosul, a Sunni-majority city that IS seized with relative ease partly amid local resentment towards the Shiite-dominated security forces.
"Depending on the intensity and scope of the fighting, as many as one million people may be forced to flee their homes in a worst-case scenario," O'Brien said in a UN statement yesterday.
Indeed, children and elderly are among those at greatest risk, he said.
"Tens of thousands of Iraqi girls, boys, women and men may be under siege or held as human shields. Thousands may be forcibly expelled or trapped between the fighting lines," O'Brien added.
US Secretary of Defence Ash Carter said the operation was key to defeating the jihadist group.
"This is a decisive moment in the campaign to deliver ISIL a lasting defeat," Carter said in a statement.
"We are confident our Iraqi partners will prevail against our common enemy and free Mosul and the rest of Iraq from ISIL's hatred and brutality.""
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