Three missiles struck a house and vehicle linked to militants at Darazinda village, 40 kilometres northeast of Miranshah, the main town in North Waziristan region, they said. Noor Khan, a resident in the village, said he saw drones in the sky before the strike.
The drone fired one missile on two militants riding on a motorbike and when two of their colleagues rushed towards them, two more missiles were fired, a security official told AFP. All four militants were killed.
The attack was the second within 24 hours in the region.
Four people were killed on Sunday when a drone fired two missiles at a vehicle travelling in the lawless tribal region.
US missile strikes have killed about 100 militants since September 3 in the rugged tribal belt.
Intelligence officials have said most of this months strikes have targeted forces led by Jalaluddin Haqqani, an Afghan commander whose forces are one of the greatest threats to foreign troops in Afghanistan.