The Pentagon said it could not yet confirm the death of Abu Muhammad al-Adnani but announced that coalition forces had carried out a "precision strike" targeting him near Al-Bab, a Syrian town near the Turkish border.
"We are still assessing the results of the strike, but al-Adnani's removal from the battlefield would mark another significant blow to [Daesh]," Pentagon spokesman Peter Cook said in a statement.
Al-Adnani was Daesh's charismatic director of external operations and its main propagandist. He served as its No. 2 leader but was at the top of the US's Daesh kill list, with a $5 million bounty on his head.
Earlier in the day, a US military intelligence official had told NBC News that al-Adnani was wounded several days ago and succumbed to his injuries in Al-Bab.
It was not clear which country's forces killed him. Turkish air forces have been operating in the area, and the US has been providing intelligence on targets to Turkey under a program called "Nomad Shadow," the military intelligence official said.
Al-Adnani was one of Daesh's longest-serving leaders, best known for issuing an edict for lone wolves to kill Westerners in September 2014.
"There is a large amount of evidence suggesting that he was tremendously influential in terms of pushing individuals in Western countries to carry out homegrown terrorist attacks," said Evan Kohlmann of Flashpoint, an NBC terrorism analyst.
"He is one of the top figures in Daesh. He is very closely associated with Daesh terrorist operations abroad."
Al-Adnani was one of the first foreign fighters to oppose US Coalition Forces in Iraq after he crossed the border from his native Syria in 2003.
He swore allegiance to Abu Musab al-Zarqawi, the Al Qaeda in Iraq leader later killed by US fighter-bombers. He reportedly was captured in 2005 and taken into custody at a camp run by the US military, but was freed in 2010.
After his release, he became the chief spokesman for Daesh, and by 2014 he had assumed a top operational role. The US declared him a "specially designated global terrorist" in August 2014.
His death comes less than six months after two other top Daesh officials — finance minister Haji Iman and No. 3 Omar al-Shishani — were killed.
"This is a really big blow for Daesh," said Laith Alkhouri, co-founder of Flashpoint. "It's not going to be what breaks its back but it could break the morale of fighters who idealized him so much."