Nagao Kagenaga served as a bushō during the late Muromachi and Sengoku periods.  Kagenaga served as the kasai, or head of house affairs, for the Yamanouchi-Uesugi family.  Kagenaga was the lord of the Kannō Castle in the Ashikaga manor of Shimotsuke Province.

In 1469, Kagenaga was born as the second son of Nagao Kagehito.  When his father died, Kagenaga was still young.  His older brother, Nagao Sadakage, then died of illness so, at the age of seven, Kagenaga inherited the headship of the Ashikaga-Nagao clan under the guardianship of his uncle, Nagao Fusakiyo.

In 1487, Fusakiyo colluded with Uesugi Sadamasa of the Ōgigayatsu-Uesugi family, triggering an assault against Kannō Castle by Uesugi Akisada, the head of the Yamanouchi-Uesugi family and the deputy shōgun of the Kantō.  This marked the outbreak of an internal conflict in the Uesugi clan known as the Chōkyō War.  In 1495, when Yokose Narishige attacked Iwamatsu Naozumi, Kagenaga came to his aid.

That same year, Kagenaga participated in lieu of Nagao Akitada, the kasai, in the coming-of-age ceremony for Ashikaga Takamoto and received the honorary title of Governor of Tajima.  The fact that Kagenaga attended this coming-of-age ceremony for the family of the Koga kubō which ordinarily the kasai would have attended suggests the significance of Kagenaga’s influence at the time.  Around this time, he exercised the powers of the head of the clan.

In 1504, after the death of Fusakiyo at the Battle of Tachikawa-no-hara, Kagenaga finally became independent as the head of the clan.  In 1510, following the demise of Uesugi Akisada, Uesugi Norifusa and Uesugi Akizane fought over the position as the head of the Yamanouchi-Uesugi family as well as the role of deputy shōgun of the Kantō.  At this time Kagenaga joined Yokose Kageshige in support of Norifusa and engaged in battle against Narita Akiyasu and Nagao Akikata, toppling the base of Akizane at Hachigata Castle.  After the victory by Norifusa, Kagenaga was appointed in lieu of Akikata to serve as the kasai for the Yamanouchi-Uesugi family.  These events occurred in connection with the Eishō Conflict.

Kagenaga was a skillful painter.  His personal portrait is kept at the Chōrin Temple that he built, in addition to landscape pictures resembling those from an Muromachi period monk and artist named Shōkei who produced India-ink paintings representative of the Kantō.  Kagenaga also had friendly relations with Kanō Masanobu, a renowned artist and school of art from the Muromachi period.