Hosokawa Mototsune served as a bushō and shugo daimyō during the Sengoku period.  He was the head of a shugo family of Izumi Province and the eighth head of the upper Hosokawa-Izumi family (known as the Hosokawa-Gyōbu family).  Mototsune served as the lord of the Katsuryū Castle in Yamashiro Province.

In the early Muromachi period, two illegitimate branches of the Hosokawa clan inherited the role of shugo, or military governor, of Izumi Province.  The founders of these two families were Hosokawa Yoriari and Hosokawa Motoyuki.  Yoriari was the first head of the upper shugo family while Motoyuki was the first head of the lower shugo family.  Mototsune was affiliated with the upper shugo family.  Notwithstanding the nomenclature of upper and lower, the families did not each govern one-half of the province but, rather, engaged in the joint governance of the province as a whole.  Despite being a narrow province, the metropolis of Sakai evolved during the Nanbokuchō period as a key harbor and commercial center in Kinai so joint governance ensured a balance in the distribution of power.

In 1482, Mototsune was born as the lineal heir of Hosokawa Motoari.  In 1500, his father was killed in battle against Hatakeyama Hisanobu so Mototsune inherited the headship of the upper Hosokawa-Izumi family.  Mototsune, together with Hosokawa Masahisa, the head of the lower Hosokawa-Izumi family, both opposed a demand from a noble named Kujō Masamoto for the return of the Hineno manor.

In the summer of 1507, Hosokawa Masamoto, the deputy shōgun, was assassinated by supporters of one of Masamoto’s adopted sons, Hosokawa Sumiyuki, including Kōzai Motonaga and Yakushiji Nagatada in the Lord Hosokawa Incident. The day after the assassination of Masamoto, Hosokawa Sumimoto was also attacked at his residence by retainers of Sumiyuki, whereupon he fled with Miyoshi Yukinaga to Aochi Castle in Ōmi Province.  The men escaped with the assistance of Yamanaka Tametoshi of Kōka.  Several months later, Sumimoto drew on the support of kokujin in Ōmi to launch an attack in Kyōto, killing Sumiyuki and his supporters.  The following day, Sumimoto had Ashikaga Yoshizumi, the shōgun, recognize his succession to the Hosokawa-Keichō family.  Nevertheless, these events divided the Keichō-Hosokawa clan with one faction supporting Sumimoto and the other faction backing Hosokawa Takakuni. This led to a prolonged succession struggle known as the Conflict between the Hosokawa and, in a broader context involving the Ashikaga shōgun family, the Eishō Disturbance.

Mototsune sided with Sumimoto and, together with Ashikaga Yoshizumi, Hosokawa Masakata, and Hatakeyama Hisanobu, battled against Takakuni and his supporters but was defeated and lost his position as the military governor of Izumi.  Takakuni sent a member of his own faction to serve as the military governor of Izumi but Mototsune fled along with Sumimoto to Awaji and Awa provinces to continue the resistance.  In 1511, Mototsune obeyed orders of Yoshizumi and Sumimoto to travel to Kyōto but was defeated at the Battle of Funaokayama and narrowly escaped with his life to Awa.  As a result, the Matsura clan serving as deputy military governors in Izumi demonstrated their independence of Mototsune and temporarily switched their allegiance to Takakuni’s faction.

After the death of Sumimoto in the sixth month of 1520, Mototsune supported Sumimoto’s lineal heir, Hosokawa Harumoto.  The Conflict between the Hosokawa finally came to an end in 1531 when Harumoto, defeated Takakuni in the Collapse at Daimotsu.  Mototsune then received permission from Harumoto to return to his position as the military governor of Izumi.  Thereafter, Mototsune continued to support Harumoto’s faction, frequently traveling from Kyōto to Izumi to suppress opposition elements in his territory.  During the Tenbun era (1532 to 1555), Mototsune’s son, Gorō Harusada of the upper Izumi shugo family resided in Izumi whereas Mototsune was based in Kyōto so it is surmised that Mototsune transferred the headship of the family and role as the military governor to Gorō from early on.  Meanwhile, Mototsune’s eldest son, Hosokawa Motoharu, was illegitimate so could not become his heir and started a cadet family instead.

From 1543, Takakuni’s adopted son, Hosokawa Ujitsuna, resisted Harumoto.  Mototsune joined Harumoto to fight against Ujitsuna but, in 1549, a senior retainer of Harumoto, Miyoshi Nagayoshi, defected from Harumoto to Ujitsuna and defeated Harumoto at the Battle of Eguchi.  As a result, Nagayoshi seized the territory of the Hosokawa clan.  From around this time, references to Harusada disappear from records so it is uncertain whether he was still alive.  Owing to the fall of the Hosokawa clan, Mototsune was ousted by Nagayoshi and accompanied Ashikaga Yoshiteru to flee to Ōmi Province.

On 6/16 of Tenbun 23 (1554), Mototsune died at the age of seventy-three.  He was succeeded by his nephew, Hosokawa Fujitaka (later known as Hosokawa Yūsai), as an adopted son.  Fujitaka was the natural son of Mototsune’s younger brother, Mitsubuchi Harukazu.  Under an alternate theory, it is noted that when Fujitaka was adopted in 1538, Harusada appeared to be serving as the head of the clan so Fujitaka may have been adopted by Harusada.  The more recent prevailing view is that Fujitaka was not adopted by either Mototsune or Harusada and instead was adopted by Hosokawa Haruhiro, a direct retainer of Ashikaga Yoshiharu, the eighth shōgun of the Muromachi bakufu.

The death of Mototsune marked the end of the governance of Izumi by the upper Hosokawa-Izumi family.