Despite not having a parliamentary mandate to take military action in Syria, Cameron told lawmakers that, as an act of self-defence, Briton Reyaad Khan had been targeted and killed in a precision drone strike in the country.
Cameron said the strike was carried out by a British Royal Air Force (RAF) remotely-piloted aircraft in August and that two people travelling with the man, including another Briton, Ruhul Amin, were also killed.
"There was a terrorist directing murder on our streets and no other means to stop him," Cameron said. "We took this action because there was no alternative."
British warplanes have launched regular air attacks against Daesh fighters in neighbouring Iraq in recent months and flown drones over Syria to gather military intelligence. But unlike some countries in a U.S.-led international coalition, it does not generally target Daesh in Syria.
""There was a terrorist directing murder on our streets and no other means to stop him," Cameron said. "We took this action because there was no alternative.""
The Royal United Services Institute (RUSI) think tank said the strike marked a big departure in policy.
"The point is not so much that this man was British but that he was targeted in an area that the UK does not currently regard, legally, as an operational theatre of war for UK forces," said RUSI Director General Michael Clarke in a statement.
Reyaad Khan, 21, from Cardiff, (left) and Ruhul Amin, from Aberdeen, (right) appeared together in an ISIS recruitment video last year aimed at luring Terrorists to Syria and Iraq
Khan, from the Welsh capital Cardiff, and Amin from Aberdeen in Scotland had their assets frozen by Britain's finance ministry last year after reports they had been involved in terrorism-related activities in Syria and appeared in a Daesh recruitment video.
"There was clear evidence of the individuals in question planning and directing armed attacks against the UK," Cameron said. "These were part of a series of actual and foiled attempts to attack the UK and our allies."