The unmanned plane fired two missiles on a house in marketplace in Miranshah, the headquarters of North Waziristan, they said.
At least four militants were killed in the attack, the officials said, adding that there was no immediate information about the nationality of those killed in the pre-dawn strike.
The officials said the militants had been using the house for some time.
Several militant groups, including Tehrik-e-Taliban Pakistan and the Haqqani Network, operate in North Waziristan, bordering Afghanistan.
It is the first drone strike in Pakistani tribal region after the Chicago conference. President Asif Ali Zardari, who attended the May 20-21 summit in Chicago, called for a halt to the American drone strikes.
Pakistan's Parliament last month passed a resolution asking US to stop drone strikes inside the country as it is violation of International law.
The US has rejected calls from Pakistan and insists that drone strikes are effective against the militants, blamed for cross-border attacks into Afghanistan.