The CIA-operated unmanned aircraft targeted a suspected militant compound and a vehicle on the border of North and South Waziristan Agency in Shawal valley.
The drone fired two missiles, killing at least six militants and injuring two others.
The identity of those killed was not known immediately but the region is infested with Taliban and al-Qaeda militants.
Pakistan opposes strikes but the US has persisted with the attacks.
Pakistan launched a full-scale military offensive in the region in June last year but militants are still active.