A US drone targeted two cars belonging to al Qaeda, killing leader Ghaleb Ahmed Baqeeti al Hadrami and four other elements of the organization.
Officials say the airstrike took place on Friday night in Mukalla, the capital of the Yemeni governorate of Hadramawt.
The drone strike also injured 10 more people.
Local sources said the al Qaeda members had weapons and ammunition in the two cars.
US jets have been targeting al Qaeda elements in Mukalla since the city fell under the control of the organization on April 2.
A number of al Qaeda leaders and elements, including Nasser al Wuhishi, were killed in a series of US raids.