Miyoshi Isan served as a bushō during the Sengoku and Azuchi-Momoyama periods and as a hatamoto during the early Edo period.  After entering the priesthood, he was called Ichininsai Isan.  The name Masakatsu appears in many materials and genealogies but this was the real name of his brother, Miyoshi Sōi, and there may be confusion in the use of names between the brothers.

Isan was born as the son of Miyoshi Masanaga from a branch of the Miyoshi clan.  He served as the lord of Enami Castle in Settsu Province.

His older brother, Sōi, was one of the members of the Miyoshi Group of Three.  The opening passage in a letter dated from the seventh month of 1571 from Ashikaga Yoshiaki (the fifteenth shōgun) to Isan refers to Sōi (also referred to as Shimotsuke-no-kami) as Isan’s older brother.

In historical accounts, the name of Miyoshi Isan first appears in a document dated 8/2 of Genki 1 (1570) to acknowledge rights to landholdings in the self-governed locale of Ōyamazaki in southern Kyōto.  His actions prior to this time are relatively unknown.  Following the death of his father, Miyoshi Masanaga, at the Battle of Eguchi, Isan is believed to have acted in concert with his older brother, Sōi (also referred to as Masakatsu).

After Oda Nobunaga marched upon Kyōto to install Ashikaga Yoshiaki as the fifteenth shōgun in the ninth month of 1568, Isan joined the Miyoshi Group of Three and Miyoshi Yasunaga to topple castles aligned with the Oda in Izumi Province.  These forces proceeded to attack Yoshiaki at the Battle of Honkoku Temple and oppose Nobunaga.  Following a defeat to the Oda army, Isan retreated to Awa Province in Shikoku and, after the death of Sōi, inherited the headship of the clan.  In the seventh month of 1570, he crossed the Seto Inland Sea and landed in Tenma in Nakajima and participated in the Battle of Noda and Fukushima Castles.

On 8/28 of Genki 1 (1570), Isan proposed surrender to Nobunaga and then joined the Oda army in a siege of the Ishiyama-Hongan Temple on Mount Hiei.  Owing to his contributions, on 9/20, Isan received from Nobunaga the Teshima District in Settsu.  In the sixth month of 1572, through an exchange of territory with Itami Chikaoki, Isan recovered his former territory of Enami.

Nevertheless, in 1572, in a conflict between Matsunaga Hisahide and Miyoshi Yoshitsugu on one side and Hosokawa Akimoto on the other side, Isan aligned with the Matsunaga forces and attacked Akimoto who was protected by Nobunaga.  This is the last account of Isan for a long period.  Meanwhile, Kōzai Naganobu (with whom Isan collaborated), allied with the Hongan Temple and died in battle in 1575.

After the Honnō Temple Incident, a coup d’état against Nobunaga on 6/2 of Tenshō 10 (1582), Isan is surmised to have served Toyotomi Hideyoshi.  References to Isan first appear again in 1592 at the time of the Bunroku Campaign in which he is referred to as an umamawari, or mounted soldier, serving in a division for the main citadel of Nagoya Castle in Hizen Province.  Following the death of Hideyoshi, from 1600, Isan served Tokugawa Ieyasu.  At the Battle of Sekigahara, he was a member of the Eastern Army, serving in a division led by Tokugawa Hidetada.  He attacked Ueda Castle in Shinano Province defended by Sanada Masayuki and his son, Sanada Nobushige, at the Battle of Ueda.

Thereafter, as a hatamoto, his fief was increased by 1,400 koku and he held 2,020 koku in three districts in Kawachi Province.  In 1604, Isan was appointed as the Governor of Inaba.  Isan also joined in the Siege of Ōsaka, and was recognized for his contributions serving as a guide on the battlefields in Kawachi, obtaining permission to engage in falconry outings and receiving valuable tea utensils.  Based on genealogical records, however, these references may have been to his son.  If the references were to Isan, then, after becoming a member of the ohanashishū, veteran retainers who accompanied their lord, he died at the age of ninety-six.  This would be an extraordinary age for this period.

Isan served as a model for Miyoshi Isan Nyūdō, one of the Ten Warriors of the Sanada.  Despite the same surname, the Isan who is the subject of this profile had no relationship with the Sanada clan.  A consort of Sanada Nobushige named Ryūseiin is considered to have been the daughter of Miyoshi Nobuyoshi (later known as Toyoyomi Hidetsugu who was adopted by Miyoshi Yasunaga), but had no connection to Isan.