Hosokawa Mochitsune served as a shugo daimyō during the Muromachi period.  Mochitsune was a member of the shōbanshū (the personal retinue of the shōgun to prepare banquets and host visitors).  He was the fourth head of the Hosokawa-Awa military family and the military governor of Awa and Mikawa provinces.

Mochitsune was born as the son of Hosokawa Mitsuhisa.  Based on family tradition, he received one of the characters from the name of Ashikaga Yoshimochi, the fourth shōgun of the Muromachi bakufu and adopted the name of Mochitsune.

In 1427, when Ashikaga Yoshimochi came into conflict with Akamatsu Mitsusuke, the military governor of Harima, Bizen, and Mimasaka provinces, Mochitsune deployed from Sanuki Province to Harima Province on behalf of his father (who was in Kyōto).  Following a pardon of Mitsusuke, Mochitsune withdrew.  As a result, it appears that he stayed in Awa at this time.

In 1430, Mochitsune was appointed as the military governor of Awa and served as a member of the shōbanshū for Ashikaga Yoshinori, the younger brother of Yoshimochi who became the sixth shōgun of the Muromachi bakufu.  From 1432 to 1433, Mochitsune participated on the side of the bakufu during a conflict between Yoshinori and the Enryaku Temple known as the Sanmon Disturbance.  On this occasion, one of Mochitsune’s vessels attempting to cross the Seto Inland Sea from Awa to Kyōto encountered stormy weather and sank resulting in the loss of over 400 soldiers from his command.

In 1440, Mochitsune, together with Takeda Nobuhide, assassinated Isshiki Yoshitsura, the head of the Tango-Isshiki clan and military governor of Tango, Wakasa, and Mikawa provinces.  As recognition for the deed, he acquired Mikawa.  In 1441, when Yoshinori headed toward the residence of Akamatsu Mitsusuke, Mochitsune accompanied him.  Yoshinori was then murdered by Mitsusuke while Mochitsune narrowly escaped from the Akamatsu residence.  Soon thereafter, Mochitsune led a large army to subdue Mitsusuke, proceeding from Settsu Province to attack Harima and converging with the army of Yamana Mochitoyo from Tajima Province, eliminating Mitsusuke.  This series of events is known as the Kakitsu Disturbance.

In 1448, Akamatsu Norinao, the nephew of Mitsusuke who had gone into hiding, killed Mitsusuke’s younger brother, Akamatsu Norishige.  For this contribution, Mochitsune, together with Ise Sadakuni (the director of the mandokoro), made a request on behalf of Norinao to Ashikaga Yoshimasa (the eighth shōgun) for the return of Harima.  This request, however, was opposed by Mochitoyo.  Through the offices of Hosokawa Katsumoto (Mochitoyo’s son-in-law and the head of the main branch of the Hosokawa), Norinao was pardoned while Mochitoyo became the lord of Harima.  Katsumoto and Mochitoyo maintained good relations but after this event the relationship between the Awa-Hosokawa family and Mochitoyo deteriorated.

On 12/16 of Hōtoku 1 (1449), Mochitsune died of illness and the age of forty-one.  He was succeeded by his adopted son, Hosokawa Shigeyuki (the natural son of Mochitsune’s younger brother, Hosokawa Norisuke).  On 12/16 of Bunmei 13 (1482), Hosokawa Masayuki (Shigeyuki’s lineal heir) hosted the 33rd death anniversary (held in the 32nd year after his death according to Buddhist tradition) while Ōsen Keisan and Tenin Ryūtaku composed tributes.

There is a theory that he suffered from an eye ailment for a long time.