Mohammed Emwazi, the Kuwaiti-born British militant, appeared in videos of the beheadings of Western hostages.
It is believed there was at least one other person in the vehicle targeted in the attack near Raqqa, in Syria.
A drone was used in the attack, according to a US official quoted by the Associated Press news agency.
A formal statement from the Pentagon stopped short of asserting that Mohammed Emwazi had definitely been killed, adding that it was assessing the operation.
Mohammed Emwazi is believed to have travelled to Syria in 2013 and later joined ISIS militants.
He first appeared in a video in August 2014, when footage was posted online showing the murder of American journalist James Foley.
Jihadi John was later pictured in the videos of the beheadings of American journalist Steven Sotloff, British aid worker David Haines and taxi driver Alan Henning, as well as American aid worker Abdul-Rahman Kassig, also known as Peter, and Japanese journalist Kenji Goto.
In each of the videos, the militant appeared dressed in a black robe with a black balaclava covering his face.
Initially dubbed “Jihadi John” by the media, he was subsequently named as Mohammed Emwazi, from west London, in February.
Earlier this year, details emerged about how Mohammed Emwazi made a number of journeys abroad before he left for Syria in 2013.
They included a trip to Tanzania in August 2009, when he is believed to have first became known to security services in the UK.
Jihadi John’s naming this year led to a row over the cause of his radicalization, with British advocacy group Cage suggesting that contact with MI5 may have contributed to it.
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