This was the fifth such strike in the country in less than two weeks.
Two Pakistani intelligence officials said the missiles hit in Dogh village near Wana, the main town in the South Waziristan tribal region.
The officials said the two militants were targeted after they came out of their suspected hideout in Dogh, about six kilometers (four miles) south of the main town of Wana. The officials spoke on condition of anonymity because they were not authorized to speak to the media.
Drone attacks in Pakistani tribal areas, where Afghan and other militants have found refuge, are considered a key tactic by U.S. officials in the war against al-Qaida and its Taliban supporters.
But most of the Pakistani public resents the strikes, which are considered an affront to the nation’s sovereignty.
The covert CIA-run program is a cause of tension between the U.S. and Pakistan.
Despite Pakistan’s demands for a halt in the drone attacks, the U.S. has fired scores of missiles into northwest Pakistan since 2008, targeting al-Qaida and Taliban operatives there. Privately, many Pakistani military officers are believed to have supported the drone program.