The Tornado jets took off from RAF Akrotiri in Cyprus, the Ministry of Defence (MoD) said.
The planes were loaded with laser-guided bombs and missiles. The Tornados were supported by a Voyager air-to-air refuelling aircraft.
The British jets would join an American-led coalition which has been pounding IS fighters in Syria and Iraq for days, trying to weaken the movement's grip on northern Iraq so the extremists can be beaten back by Kurdish and Iraqi troops.
"For operational security reasons we will not be providing a running commentary on movements; we will provide an update on activity when it is appropriate to do so."
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The action comes after Parliament voted by 524 votes to 43 to take action against IS in Iraq, but not Syria.
Six Tornado G4 fighters have been based in Cyprus since August but so far have been used only for reconnaissance. The bombers are expected to lead any British operations targeting IS.
On Friday, MPs from all three main Westminster parties voted for military action in House of Commons but stopped short of extending its support to operations in Syria.
As well as the Tornados at the British Akrotiri base in Cyprus, the RAF also has a Rivet Joint spy plane - successor to the Nimrod - in the region.
UK foreign secretary Philip Hammond said Britain was consulting with its allies to choose targets. He said he expected little resistance from the ground.
They were braced to begin strike runs with Paveway IV guided bombs and Brimstone missiles.
Military sources told 'The Telegraph' that defence chiefs were also considering launching Tomahawk cruise missiles from a Royal Navy submarine in the region.