Drone strikes are extremely unpopular among many Pakistanis because they are seen as a violation of the country's sovereignty, although leaked documents have shown that Islamabad and Washington have secretly colluded over some cases in the past.
The attack occurred in the Sara Khwa area of Kurram, one of seven so-called tribal districts that lie along the border with Afghanistan, where Pakistan has been battling a homegrown Islamist insurgency for more than a decade and a half.Requesting anonymity, a local government official described the two men who were killed as "militants" but said their identity could not immediately be confirmed.
A second official confirmed the strike and the casualties. "The drone came from Afghanistan and returned after firing two missiles on the motorbike," he said.
The last US drone attack took place in May 2016, killing the then leader of the Afghan Taliban Mullah Akhtar Mansour as well as his driver in southwestern Balochistan province.
The very first of the more than 420 attacks occurred in 2004 under the government of President George W. Bush, but it was under President Barack Obama that their use increased substantially, before tapering off in his second term. Last year there were only three.
Drones have proven extremely controversial with the Pakistani public and rights groups. In 2013, Amnesty International said the US could be guilty of war crimes by carrying out extrajudicial killings.
The strike could be read as the first hint about President Trump's policy toward Pakistan, a country he has spoken about relatively little.
In December Pakistan's foreign office said then president-elect Trump praised its prime minister Nawaz Sharif as a "terrific guy" and offered support for a "fantastic" country, in an effusive phone call that baffled many.
Trump's aides confirmed the call but gave a more toned-down account, saying the pair had a "productive conversation about how the United States and Pakistan will have a strong working relationship in the future."