It was the first in the nuclear-armed nation since US President Donald Trump took office in January.
Officials said a missile struck the two men while they were riding a motorcycle in the northwestern Kurram Agency.
"A drone missile struck the motorcycle," said village elder Haji Zamin Hussain.
The US military command in Afghanistan said its forces had not conducted any strikes in Pakistan.
A government official identified one of the men killed as Qari Abdullah Subari, a senior commander from the Afghan Taliban.
An intelligence source said the other man was also a Taliban member named Shakir.
In its last high-profile drone attack inside Pakistan, the United States in May killed Afghan Taliban leader Mullah Akhtar Mansour in the southwestern province of Balochistan.
COMMENTS (2)
Comments are moderated and generally will be posted if they are on-topic and not abusive.
For more information, please see our Comments FAQ