Tornado bombers took off from the RAF Akrotiri air base in Cyprus just hours after British lawmakers voted 397-223 to support Cameron's plan for air strikes, Reuters reported. They returned to base safely several hours later.
The four bombers used laser-guided bombs to attack six targets in the Omar oil fields in eastern Syria controlled by the militant group Daesh (ISIL).
There was no immediate information about casualties.
After 15 years in which hundreds of British troops died serving as the main battlefield ally of the United States in Iraq and Afghanistan, many in Britain are wary of more war in the Middle East.
The decision to extend bombing to Syria divided the opposition Labor Party, opposed by its leader Jeremy Corbyn but supported by its foreign affairs spokesman Hilary Benn in a passionate speech in parliament.
Russia is also bombing Syria outside the US-led coalition. Moscow supports Syrian President Bashar Assad, while the United States and its allies oppose him.
The news of the vote was met by howls of disgust by dozens of anti-war protesters demonstrating outside parliament.