The drone fired three missiles on a compound believed to be owned by the Haqqani network of Afghan Taliban in the village of Darga Mandi in Ghulam Khan Tehsil late last night.
Six suspected militants were killed whereas three others were injured in the strike, media reports said.
The CIA-operated spy plane continued its low-altitude flights in the area after the incident, local residents said.
The Foreign Ministry strongly condemned the attack and said such strikes also set "dangerous precedents in the inter-state relations".
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"Pakistan has repeatedly emphasized the importance of bringing an immediate end to drone strikes," the Ministry said in a statement.
On August 31, a US drone killed at least four militants in a missile strike targeting a compound in the village of Heso Khel, around 35 kilometres east of Miranshah.
The US has not stopped its drone campaign despite repeated protests from Pakistan, which describes the attacks as violation of its sovereignty and counter-productive for the war on terror.
Earlier, US Secretary of State John Kerry had hinted towards an end of the drone campaign in the tribal areas of Pakistan, as he said on August 1 that the signature strikes could end "very soon".
This was the first time that a senior US official had indicated that there could be a definitive end to the programme, which the CIA has in the past called an effective counter-terrorism weapon.
According to reports, a total of 565 militants have died in around 400 drone strikes in Pakistan. However, rights groups say many non-combatants have also been killed.