RAF pilots have operated drone missions over Afghanistan from British soil.
Up until this week, all such missions in the Afghan conflict had been conducted at Creech air force base in Nevada.
The UK currently has five Reaper unmanned aerial vehicles (UAVs) - also known as remotely piloted air systems (RPAS).
Prime Minister David Cameron confirmed in 2010 that the fleet of Reaper aircraft would expand.
Delivery of the new aircraft is expected this summer.
The Ministry of Defence (MoD) has confirmed the commencement of operations from Lincolnshire in a short statement.
It said: "XIII Sqn have commenced supporting ISAF and Afghan ground troops in Afghanistan with armed intelligence and surveillance missions, which are remotely piloted from RAF Waddington."
Since 2007, British drones have flown some 45,000 hours in the Afghan conflict and fired around 350 weapons.
Their primary use is for surveillance, but they do carry precision guided missiles or Hellfire missiles on board for use when necessary.
The Waddington-based squadron numbers around 100 personnel who are specifically trained to fly the aircraft.
The drones take off and land under the guidance of pilots on the ground in Afghanistan but the pilots in Lincolnshire take over once they’ve reached a suitable height. They tend to fly at an altitude of between 15,000 to 20,000 feet.
The British Government insists it only flies its fleet of UAVs in Afghanistan - a country that it has an legal remit to be in.
But drones are controversial, largely because of their use in Pakistan and Yemen by the US government and a protest march is planned outside RAF Waddington this Saturday.
The pilots in Lincolnshire are operating in conjunction with British and American colleagues still based in Nevada - this is largely based on a shift pattern to reflect the time difference and to allow for 24 hour operations.
The MoD will only confirm one incident of civilian casualties involving its aircraft, when innocent people were killed by the blast of a missile that also killed two insurgents.