The drone hit a pickup that was carrying 16 suspected militants in Hazmiah area of al-Bayda, about 268 km southeast of the capital Sanaa. Five civilians passing by in a car were also killed, Xinhua reported.
Six other civilians travelling in another car on the highway of Hazmiah area were injured, the witnesses said.
It was the seventh drone strike in the past two months.
A drone strike killed three suspected Al Qaeda militants early this month in the southern province of Abyan.
In March five separate drone strikes in al-Jawf, Marib and Shabwa killed at least six militants.