The 27-year-old, the third in line to the British throne, was called in to provide air support to troops tracking a commander-level Taliban chief and hit the target with a 100 lb Hellfire missile fired from an Apache helicopter.
It is the first time the prince has been involved in a fatal airstrike against a Taliban commander, a report in The Sun said.
According to the Daily Mail, the attack is said to have happened in late October, shortly after the prince returned to Afghanistan for his second deployment as gunship co-pilot.
A defence insider said, "We were on patrol and the Apache helicopters were called in. We heard this posh voice come over the radio and knew it was Big H. They were tracking a Taliban leader - he was commander-level."
Captain Harry Wales - as he is known in the Army - is a co-pilot gunner in the Apache unit which has the highest 'kill rate' in the war.
As the co-pilot gunner, Harry commands missions, fires the weapons, navigates and sometimes take over the controls.
The two-crew gunship - nicknamed the 'flying tank' - is used by UK forces in Afghanistan to smash the Taliban, gather intelligence and provide support for soldiers on the ground.
Harry learned to fly Apache helicopters during an 18-month training course in February.
A spokesman for the Ministry of Defence said, "We do not comment on an individual's deployment in Afghanistan."
Harry was keen to return to Afghanistan after his first tour of duty was cut short in 2008.
The prince had been secretly deployed with the Household Cavalry as a forward air controller directing bombing strikes against insurgents for ten weeks.
His time there was cut short when news of his presence was leaked on foreign websites and he was brought back to Britain.
However, Harry was so determined to do another tour of duty that he retrained as an Apache pilot in the hope it would increase his chances of being redeployed.
The prince's current tour of duty in Afghanistan is for four months and in his words, the Apache attack helicopter is simply 'awesome'.
Designed to hunt and destroy tanks, the fearsome Apache is capable of flying at 205 mph and boasts a mix of weapons including a wing-mounted aerial rocket, Hellfire laser-guided missiles and a 30 mm chain gun.