The destruction of the Temple of Bel sparked outrage and international headlines, precisely the reaction the jihadist group may have been seeking, experts said.
Dozens of relics remain at risk in the ruins of Palmyra, which IS jihadists seized from regime forces in May as they pursued their campaign for territory in Syria and Iraq.
The extremist group's harsh philosophy condemns pre-Islamic religious sites and considers statues and grave markers to be idolatrous, but it has also been accused of destroying heritage to loot items for the black market and to gain publicity.
The 2,000-year-old temple was the centrepiece of Palmyra's famed ruins and one of the most important relics at the UNESCO-listed heritage site.
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"The Temple of Bel was the most beautiful symbol of all of Syria. It was the most beautiful place to visit," Syrian antiquities director Maamoun Abdulkarim told AFP by telephone from Damascus.
"And we have lost it forever."
While antiquities staff evacuated most of the city's museum before IS arrived, the group destroyed an ornate lion statue outside the building and also mined Palmyra's ruins.
Last month the jihadists beheaded the 82-year old former antiquities chief in Palmyra and destroyed the ancient shrine of Baal Shamin.
Activists and a monitor on Sunday reported a large explosion at the site had destroyed the Temple of Bel.
Abdulkarim said Palmyra's remaining ruins, which lie in the southwest of the city, include "dozens of the greatest grave markers, the amphitheatre, and the Temple of Nabu, which only has its foundations."
But it was the scene of a gruesome massacre shortly after IS seized Palmyra, with child members of the group executing 25 Syrian soldiers in the amphitheatre.
"They have killed Palmyra. Now, they will terrorise it," Abdulkarim said. "It's the last warning before the complete destruction of Palmyra."
Cheikhmous Ali of the Association for the Protection of Syrian Archeology (APSA) described the razing of the ruins as "a way to pressure and torture the local population -- to suppress their history and their collective memory."