He has historical reputation as one of Japan's Three Great Villains (日本三大梟雄), a nickname which he shared with Ukita Naoie and Saitō Dōsan, due to their ambitious and treasonous personality, along with the habit to resort into underhanded tactics and assassinations to eliminate the oppositions.

He directed the conquest of the province of Yamato in the 1560s and by 1564 had built a sufficient power base to be effectively independent.

This left Miyoshi Yoshitsugu the adopted heir when Nagayoshi died in 1564, too young to rule.

[8] Yoshiteru's brother, Ashikaga Yoshiaki, fled and the shōgun was replaced by his younger cousin, Yoshihide.

Initially, the forces of Hisahide were unsuccessful and his apparent destruction of the Buddhist Tōdai-ji in Nara was considered an act of infamy.