Al-Adnani was the most visible figure in ISIS' core leadership, the first to declare the so-called "caliphate," and was instrumental as the group's spokesman. He is also believed to have authorized the terror attacks in Paris, Brussels and Istanbul.
According to ISIS-affiliated news agency Amaq, al-Adnani was killed while supervising battle lines in Aleppo province in northern Syria.
Despite the loss of such an important leader and a series of territorial setbacks, it is much too early to begin writing ISIS's death notice: There are plenty of opportunities for the terror group to exploit as its enemies turn on each other.
But it is under pressure on many fronts, something al-Adnani himself recognized.
In an audio message at the end of May, he asked the "crusaders": "Will we be defeated and you victorious if you took Mosul or Sirte or Raqqa or all the cities -- and we returned as we were in the beginning? No, defeat is losing the will and the desire to fight."
Latest in a long line of leaders killed
ISIS has lost plenty of leading figures in the last 18 months -- many of them to US drone strikes as intelligence on the movements of the group's hierarchy has improved.
Among those targeted recently are Sami Jassim Mohammed Al-Jabouri, a.k.a. Haji Hamad
, who oversaw ISIS's oil resources; Afiz Sayed Khan
, the organization's leader in Afghanistan, and military commander Omar al-Shishani
But the loss of al-Adnani is a severe blow. He'd been the group's emir in Syria for more than three years, had a high public profile and a leading role in organizing plots to attack Western Europe.
"He's been somebody that has inspired a wave of terrorism around the Western world, putting out fatwas, calling for attacks on just about anybody, anywhere, anyhow, by guns, knives, automobiles," says CNN's terrorism analyst Paul Cruickshank.
Al-Adani was one of ISIS chief Abu Bakr al-Baghdadi's key deputies, a founding member of the terror group, and it is thought he will be a difficult person to replace.
Even though ISIS remains a resilient outfit with what might be called a deep bench, his death comes at a critical time for the group.
ISIS losing ground in Iraq, Syria
ISIS' core territory in Iraq and Syria has continued to shrink over the last month. ISIS has lost some 15% of the land it held at the beginning of the year and its affiliates in both Libya and the Sinai desert in Egypt have also suffered setbacks.
Over the past month, the Iraqi army and Kurdish Peshmerga forces have chipped away at ISIS' control around Mosul, the largest city it controls and the place where ISIS leader Abu Bakr Al-Baghdadi declared the "caliphate" two years ago.
The expulsion of ISIS from the town of Qayyarah by Iraqi security forces further fragments the territory it holds in the area. The Peshmerga claim to have recovered several villages and about 100 square kilometres of territory to the east of Mosul.
Iraqi Prime Minister Haider al-Abadi has promised Iraqis that Mosul will be liberated this year, but that will require a coordination of multiple forces and a plan for governance.
In Syria, the rebel Syrian Democratic Forces finally drove the remnants of an ISIS presence from the town of Manbij, a critical way station between Raqqa and the Syrian border (and not far from where al-Adnani was killed.) Hundreds of ISIS members fled north to the border town of Jarablus on the Syrian border -- only to flee again weeks later when the Turkish-led incursion into northern Syria began.
Gen. Joseph Votel, commander of the US Central Command, told reporters at the Pentagon that al-Baghdadi had told fighters in Manbij "to fight to the death."
"They didn't," Votel said, questioning how much command and control ISIS leadership has over its fighters.
Under attack in Sinai, Libya
In Libya, the last pocket of ISIS resistance is clinging on in the coastal city of Sirte, attacked on the ground by militia that support the nascent Libyan government and from the air by US airstrikes.
However, kicking ISIS out of Sirte may be a double-edged sword. Its fighters have scattered to the south, but the many Tunisians among them may return home to launch more terror attacks there, according to a new United Nations report.
In the Sinai desert, where the ISIS affiliate Ansar Bait al-Maqdis has inflicted hundreds of casualties on Egyptian security forces, military operations appear to be having some success.
In August, the Egyptian army claimed to have killed Abu Duaa al-Ansari, a senior leader of the group, and a number of his aides in airstrikes targeting their stronghold. (http://edition.cnn.com/2016/08/04/middleeast/egypt-kills-isis-leader/index.html)
Running out of cash?
The US estimates that ISIS brought in $1 billion in revenue in 2015, but attacks on their oil infrastructure and cash holdings are believed to be putting a squeeze on the terror group's finances.
Airstrikes by the U.S.-led coalition against ISIS cash storage sites in Iraq and Syria are reported to having destroyed "possibly" more than $100 million of the group's money.
A US official, Adam Szubin, whose role at the Treasury includes pursuing terrorists' sources of money, says the group is under growing financial pressure.
In an interview last month with the Combating Terrorism Center's Sentinel, he said, "We've seen allegations to the tune of millions of dollars being embezzled by ISIL leaders as their resources have shrunk."
Letting others fight their battles?
Amid fast-moving events in northern Syria in recent weeks, one surprise was the speed with which ISIS retreated from Jarablus
- a crucial conduit for supplies and fighters. After weeks of resistance in nearby Manbij, hundreds of ISIS fighters slipped out of Jarablus within hours of the incursion by Turkish forces
Perhaps they decided that resisting Turkish tanks and US airpower was pointless. But ISIS' leadership may also have calculated that the Turks' real target was the Syrian Kurdish militia -- the YPG.
A weaker Kurdish resistance would suit ISIS just fine. An expanding conflict between the YPG and Syrian rebel factions supported by Turkey would relieve some of the pressure on Raqqa, the largest town in Syria still held by ISIS.
The United States has urged both Turkey and the YPG to focus their attacks on ISIS, and a tenuous truce appears to have taken hold. But there is little love lost between rebel factions supported by Turkey and those that joined the YPG under the US-supported umbrella of the Syrian Democratic Forces.
Columb Strack, a senior analyst at IHS Jane's, says ISIS' "main objective here is to maintain the remaining informal smuggling routes across the Turkish border, and the town of al-Bab, which acts as a logistics hub for that. Losing access to the Turkish border would make the Islamic State's governance project unviable."
New Mideast fronts in ISIS war
ISIS will be hoping for more clashes between the Kurds and the Syrian regime after the sudden flare-up in Hasakah last month, so it can take advantage of how thinly spread the YPG is.
ISIS also appears to be probing a new front in southern Syria, close to the Jordanian border. In late June it carried out a suicide bombings against Jordanian soldiers on the border.
Last week, it launched a complex attack against a rebel group's base where the borders of Jordan, Syria and Iraq meet. It can still carry out offensive operations on a wide number of fronts.
ISIS will continue to take advantage of a fluid battlefield and the weakness of its enemies where it can. It will continue trying to co-opt and coerce other Islamist factions and tribes, especially in Syria.
Eye on Western targets
Across the globe, ISIS and its affiliates are beginning to look more like a traditional terror network and less like wilayat, or provinces of the caliphate, as they are grandiosely described.
And there is serious concern that the loss of Al-Adnani will provoke the group's fighters to avenge his death with retaliatory attacks in the West -- Europe, Russian cities, even the United States -- like those he inspired in France, Turkey and Belgium.READ: Mapping ISIS attacks around the world
"In the medium to long term, any time you take out the driving force behind ISIS's international attack planning, that is going to be a big positive for all our safety, frankly," says Cruickshank. "But in the short term there is concern that some of ISIS's attack planning may be accelerated."
More often than not, such attacks will be carried out by individuals (as was the case in Nice
) with a complex mix of personal and religious grievances who adopt the ISIS brand late in the day.
But as its core territory shrinks, ISIS will celebrate them with desperate glee.