The interior ministry said Qassem al-Rimi, the military boss of al-Qaeda in the Arabian Peninsula (AQAP), died when a missile hit his vehicle in the eastern part of Saada province on Friday.
Also killed were Ayed al-Shabwani, Ammar al-Waili, Saleh al-Tais, Ibrahim Mohammed Saleh al-Banna and an unidentified sixth person, the ministry said in a statement on its website.
Rimi was among 23 people who had made a daring escape from a state security prison in Sanaa, the capital, in February 2006, and he was on a list of 152 wanted suspects.
Banna, also known as Abu Aymen al-Masri, was said to be an "ideologist" of the group.
Yemen is under US pressure to clamp down on al-Qaeda and analysts say that the government in the impoverished state is keen to show the world it can crush al-Qaeda fighters on its own.
Said Ali Obeid al-Jamhi, a regional political analyst, said that for Sanaa, the "successive and successful strikes carried out since December 17 prove that logistical and intelligence assistance is more effective" than direct intervention by foreign forces.
The council of Yemeni clerics warned on Thursday of jihad, or holy war, if there is any foreign military intervention in the country.
An international conference on Yemen will be held in London on January 27.