The airstrike, likely carried out by an unmanned aircraft operated by the CIA, hit a vehicle carrying a dozen members of al Qaeda in the Arabian Peninsula (AQAP) in Abyan province in southern Yemen, according to the Associated Press.
AQAP, the terror group's Yemen cell, is considered by American military and intelligence officials as the most active and violent among the group's various terror cells.
The vehicle transporting the al Qaeda fighters was a truck stolen from a Yemeni army outpost by AQAP members during the ongoing fighting in the south. All 12 terrorists were reportedly killed in the airstrike.
News of the airstrike comes during a massive counterterrorism operation being waged by Yemeni military forces.
The fighting broke out Monday around the southern Yemen town of Lawder after al Qaeda forces ambushed a nearby military outpost.
Clashes between Yemeni troops and AQAP fighters on Wednesday left 31 people dead, including 28 militants, according to reports.
That raises the death toll from three days of clashes to at least 158, military officials told the AP.
Monday's airstrike comes less than a month after American and Yemeni warships bombarded the terror group's hideouts in the coastal cities near the southern town of Zinjibar.
Military officials claim 29 AQAP were killed during the alleged joint operation between U.S. and Yemeni forces on March 23, according to reports by Radio Free Europe and Al-Arabiya.
The naval bombardment took place days after Ansar al-Shariah, a jihadist group tied to AQAP, claimed to have shot and killed American Joel Wesley.
The U.S. Navy has denied any involvement in the shelling of suspected al Qaeda targets in Abyan.
No American warships from the service's Fifth Fleet or elsewhere in the region were involved in those operations, service officials told The Hill in March.
The Fifth Fleet is home to the Navy's Central Command and is headquartered in Bahrain.
American unmanned drones reportedly took out 25 al Qaeda fighters during a March 10 raid in the southern Yemen town of Bayda, southeast of the country's capitol Sanaa, Reuters reported at the time.
The Pentagon confirmed that U.S. fighters also hit Abyan in a second round of airstrikes a day after the Bayda raids, targeting suspected militants in the province.