The unmanned aircraft struck the motorcycle carrying the men in Bayda province at around midnight Friday, the official told AFP.
"The strike targeted two Al-Qaeda militants, local commander Abu Hussein Al-Theriya and another, Dawoud Al-Sanaani, as they rode through the province," he said.
Although the US only sporadically reports on its long-running bombing campaign against Al-Qaeda in the Arabian Peninsula (AQAP), it is the only force known to operate armed drones over Yemen.
The drone war has intensified since President Donald Trump took office.
Washington also backs ally Saudi Arabia in its military intervention in Yemen, launched in 2015 with the aim of forcing Iran-backed rebels from the capital and restoring the government to power.
AQAP and Daesh have flourished in the chaos of the conflict.