One US official, speaking on condition of anonymity, said the strike likely killed Mohammed Emwazi, a British citizen, but cautioned that it was too soon to make any determination.
The Pentagon said it was still assessing the effectiveness of the strike in the Syrian city of Raqqa, the de facto capital of Islamic State.
If his death is confirmed, it would be an important milestone in the US-led campaign against the group and would come more than a year after US President Barack Obama promised justice after the deaths of American hostages.
Dressed entirely in black, a balaclava covering all but his eyes and the bridge of his nose, “Jihadi John” became a menacing symbol of Islamic State brutality and one of the world’s most wanted men.
Emwazi participated in videos showing the killings of US journalists James Foley and Steven Sotloff, US aid worker Peter Kassig, British aid workers David Haines and Alan Henning, Japanese journalist Kenji Goto, and other hostages.
Kassig, from Indiana, was also known as Abdul-Rahman, a name he took after converting to Islam in captivity.
Emwazi used the videos to threaten the West, admonish its Arab allies and taunt Obama and British Prime Minister David Cameron in front of petrified hostages cowering in orange jump suits.
“We are assessing the results of tonight’s operation and will provide additional information as and where appropriate,” said Pentagon spokesman Peter Cook.
It was not immediately clear how long it might take for a final determination.
The first U.S. official said the operation itself had been in the works for days. Still, key details remained unclear, including how the United States tracked Emwazi down and how it planned the operation.
The strike came just as the United States seeks to increase pressure on Islamic State fighters, who have seized parts of Syria and Iraq, and who Obama has vowed to defeat.
The pressure includes US plans to deploy dozens of special operations forces to Syria, deliver more weaponry to US-backed Syrian fighters and to thicken US air strikes against the militant group.