The destruction of the UNESCO world heritage site was reported two days after the Iraqi antiquities ministry said that IS bulldozed the ancient Assyrian city of Nimrud, and a week after the jihadists released a tape of them smashing artefacts in the Mosul museum.
"The destruction of Hatra marks a turning point in the appalling strategy of cultural cleansing under way in Iraq," UNESCO Director General Irina Bokova said.
Hatra is an extremely well-preserved city with a unique mix of eastern and western architecture, located in a desert area about 60 miles (100 kilometres) southwest of the northern jihadist hub of Mosul.
"Official sources today reported the destruction of the World Heritage property of Hatra," the organisation said in a statement.
The UNESCO statement did not say when or how Hatra, which was built around 2,200 years ago, was destroyed, nor was any Iraqi official able to provide such details.
Mohammed Nuri, an MP from southern Nineveh province, where Hatra is located, said that "until this moment, there are no confirmed reports that Hatra has been destroyed."
"Hatra is somewhat isolated, and residents are not nearby," he said. "I have not heard of someone who physically saw the destruction taking place."
A statement from Iraq's tourism and antiquities ministry also condemned the destruction of the city, but it only cited media reports and did not directly confirm the incident.
- Arab capital -
However, after smashing statues in the Mosul museum and at an archaeological site in the city, IS militants reportedly warned a guard that they would go on to destroy Nimrud and Hatra.
But razing the entire site of Hatra, whose thick walls and large buildings withstood two Roman invasions in the 2nd century, would be no small undertaking.
UNESCO describes Hatra as "a large fortified city under the influence of the Parthian Empire, the capital of the first Arab kingdom, and bearing the roots of Islamic Arab cities."
"This is a direct attack against the history of Islamic Arab cities, and it confirms the role of destruction of heritage in the propaganda of extremist groups," Bokova said.
Signup to our newsletter and follow us on Facebook and Twitter!
She co-signed the statement with Abdulaziz Othman Altwaijri, Director General of the Islamic Educational, Scientific and Cultural Organisation (ISESCO).
The jihadists try to justify the destruction by saying the statues and sites are idolatrous, but experts say they traffic antiquities to fund their self-proclaimed "caliphate" and destroy only those pieces that are too bulky to be smuggled.
The timing of the attacks also indicates that they are more for propaganda than religious purposes, as there were more than eight months in which the militants controlled the areas where the sites are located.
"This is part of their propaganda, it is designed to shock us," said Eleanor Robson, professor of ancient near eastern history at University College London.
- Powerless -
The Islamic State group, which conquered nearly a third of Iraq virtually unopposed nine months ago, has built a reputation as the most violent group in modern jihad by beheading and crucifying its victims in public or on tape.
But Iraq's allies, led by the United States and Iran, have since come to the rescue and helped organise a major counter-offensive that is steadily shrinking IS' footprint.
After being forced out of the province of Diyala earlier this year, the jihadists are now fighting off a huge assault on the city of Tikrit as government and allied forces continue to work their way north towards the main IS stronghold of Mosul.
The spate of attacks on heritage sites in a region described as the cradle of civilisation has sparked a global outcry and drawn comparisons with the 2001 dynamiting by the Taliban of the Bamiyan buddhas in Afghanistan.
Hatra is one of only four UNESCO world heritage sites in Iraq and one of its most famous archaeological treasures.
"It was ruled by Arab kings and thrived as a major staging post along the famous Silk Road of ancient times linking the East to Palmyra (in Syria) and further on to the shores of the Mediterranean," said Ihsan Fethi, an Iraqi architect and heritage expert.
The archaeological world had been resigned to the prospect of Hatra's destruction.
"Now we are confronted with our worst fears –- a senseless and fanatical campaign of destruction and about which we can do very little," Stuart Gibson, a UNESCO expert on museums, had told AFP before reports of Hatra's destruction.