Gavin Williamson also announced an upgrade to the UK's Typhoon fleet during a visit to unveil a new F-35 hangar.
Together, the F-35B and Typhoon will form part of the UK's combat air fleet, interoperability which the RAF says has been tested in operational trials.
New weapons such as the air-to-air missile Meteor, deep strike cruise missile Storm Shadow and precision attack Brimstone missiles have been fitted to the Typhoon under the multi-million pound Project Centurion, which began in 2015.
The Defence Secretary made the announcements in front of four different aircraft in a brand-new maintenance hangar at RAF Marham.
The hangar was opened along with a state-of-the-art new training centre - facilities which, along with resurfaced runways and new landing pads, have been installed to accommodate the F-35B's ability to land vertically.
Defence Secretary Gavin Williamson said: "As we bid farewell to the RAF's first century, we are setting our sights on the next 100 years.
"Our nation is moving into a new era outside the EU, and our huge achievements in air capability make our commitment to a role on the world stage clear to both our allies and our enemies.
"The incredible F-35 jets are ready for operations, a transformed Typhoon has the power to dominate the skies into the 2040s and we continue to look even further into an ambitious future.
"The RAF has long shown Britain at its great and global best, and today it lifts our nation to even greater heights."
There are currently 17 aircraft in the F-35 fleet, with 18 more in build or on order.
The Ministry of Defence said the jets will be jointly manned by the RAF and the Royal Navy and can operate from land and sea, forming part of a Carrier Strike Group when operating from the Queen Elizabeth-class aircraft carriers.
On display at RAF Marham was an F-35, a Tornado, which is being retired later this year, and a Typhoon, the jet to which the Tornado's capabilities have been transferred.
There was also a model of the Tempest fighter jet on show.
Chief of the Air Staff Air Chief Marshal Sir Stephen Hillier said: "I am proud to confirm that the RAF’s Combat Air capability has taken yet another significant step towards the realisation of our Next Generation Air Force.
"With its cutting-edge stealth technology, our F-35s are now ready to deploy on operations and, alongside our combat-proven Typhoon, offer a step-change in our ability to employ air power around the world.
"Furthermore, the successful integration of Stormshadow, Brimstone and Meteor on Typhoon completes and enhances the transition of world-class capabilities from Tornado and allows a stalwart of the RAF’s Combat Air inventory to retire from service.
"The successful attainment of these milestones and the potential offered by Project Tempest will continue to assure the RAF’s ability to protect the nation, defend the United Kingdom’s interests and support the national prosperity agenda now and well into the future."