RAF Typhoon FGR4s have operated alongside French warplanes in a combined operation against an underground arms cache in Syrian territory operated by the IS group, per a report from the UK's MoD.
The location, located using surveillance, was assessed as storing arms and explosives, the release indicated, and was positioned in mountainous terrain just above Palmyra in the heart of Syria.
"The RAF jets used Paveway IV guided bombs to hit a several entry passages down to the depot... early reports suggest the strike was effective," the ministry announced.
There was no evidence of any civilian impact in the attack late on Saturday and all the aircraft returned safely, the MoD added.
The British jets were supported by a Voyager aerial refuelling aircraft.
IS - referred to as the so-called Islamic State - established jihadist rule over parts of Iraq and Syria until 2019.
"This strike demonstrates our UK leadership, and determination to operate in unison with our allies, to eradicate any re-emergence of IS and their harmful and extremist ideologies in the area," UK Defence Secretary the minister said.
RAF aircraft have conducted surveillance missions over Syrian airspace to "forestall any attempted comeback" of Islamic State subsequent to its military defeat at the battle of Baghuz in 2019, the ministry said.
"I extend gratitude to all the members of our armed forces who took part in this mission for their expertise and their valour," Healey said. "They were among a great many UK service members on duty over the festive period. This action, to eliminate militants who endanger our security, demonstrates how our armed forces are always on standby, continuously, protecting the UK within its borders and powerful internationally."
In December, the US military carried out what it described as a "large-scale strike" targeting Islamic State objectives in the country, subsequent to an ambush killed two American soldiers and a local interpreter in Palmyra.
The United Nations reports IS still boasts an estimated 5,000 to 7,000 militants in Iraq and Syria.
