The missions follow a "successful training period in Cyprus", Exercise Lightning Dawn, which sought to build capability for the F-35 and supporting elements.
A release from the MoD said, "Due to the exceptional performance of the aircraft, pilots and support staff during this time, it was decided that they were ready to make their operational debut from RAF Akrotiri, alongside the Typhoons."
"The F-35s are the most advanced jets our country has ever possessed and will form the backbone of British air defence for decades to come," UK Defence Secretary Penny Mordaunt said.
"They have passed every test their training has thrown at them with flying colours and their first real operational mission is a significant step into the future for the UK."
The first sorties for the RAF F-35Bs were flown last week in support of Operation Shader, the UK's contribution to the counter-Daesh mission in Iraq and Syria.
Two aircraft conducted a patrol over Syria for that sortie, with 12 more being completed since.
"It’s great to see our F-35B Lightning jets already proving themselves on operations so early in their life cycle, ably demonstrating the fantastic capability these world-leading aircraft offer," Admiral Tony Radakin, CB, ADC, First Sea Lord and Chief of Naval Staff, said.
"This Autumn, our aircraft carrier HMS Queen Elizabeth will return to the east coast of the United States to conduct Operational Trials with our Lightning Force, taking this fifth-generation capability to the next level as they prove their ability to operate from the sea.
"For decades to come, this exciting new combination of aircraft carriers and F-35B Lightnings will provide a potent, globally deployable carrier strike capability, a powerful conventional deterrent and the centrepiece of our country’s expeditionary forces."
The UK currently owns 17 F-35B aircraft, and will conduct trials later in the year for their capability at sea.
The UK plans on procuring 138 aircraft over the life of the F-35 program.