Four Brimstone missiles were deployed on two missions, British Prime Minister David Cameron's Downing Street office has confirmed.
The Brimstone missile was used by the UK government to strengthen its case in the run-up to the vote in the House of Commons on extending airstrikes to Syria as being a unique British contribution.
The ministers said that the missile's accuracy meant that it was better placed in helping to avoid civilian casualties.
One missile was used against enemy positions near the ISIS de-facto capital Raqqa, including targeting an ISIS vehicle.
There were also three other RAF missions inSyria that did not use Brimstone missiles, including striking enemy tunnels near Raqqa.
Cameron's spokesperson said: "This is part of the ongoing operation and work we are doing with coalition partners to defeat Daesh (Arabic name for ISIS) in Iraq and Syria. We have always been clear that it is going to take time and require patience and persistence, but it reflects the fact that where we identify targets and an ability to strike them, we will do all we can to tackle Daesh."
The UK's ministry of defence (MoD) said there were a number of missions over Iraq last week, supporting troops on the ground, including destroying two machine-gun positions and two armoured personnel carriers near Ramadi.
UK defence secretary Michael Fallon said: "Britain is playing a key role in the fight against Daesh, whether helping Iraqi ground forces retake Ramadi or by striking targets near its Raqqa heartland."
"Our Reaper drones have now flown 1,000 missions against Daesh and we will maintain this tempo with RAF pilots flying day and night over Iraq and Syria. The Royal Navy continues to support our allies as HMS St Albans will shortly join the Charles de Gaulle aircraft carrier group as we unite to destroy Daesh," Fallon said.
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