His eighth generation descendant Yoshinaga settled in the district of Miyoshi (Awa province) and took the name of the place.

Though they would fade from prominence, the Ogasawara, a clan closely related to them, would continue as a major political force throughout the Edo period.

[4] In the Muromachi period, Miyoshi Yukinaga [ja], dubbed a great commander having both wisdom and courage, served the Hosokawa clan as Shogunal Deputy.

After the death of Yukinaga, his grandson Motonaga [ja] supported the young lord Hosokawa Harumoto.

Motonaga made achievements by helping Harumoto become kanrei, and he ended up being the influential power in the Hosokawa clan.

However, he married a daughter of Yusa Naganori, who was the shugodai of Kawachi Province and had a strong influence in the Kinki region.

Nagayoshi defeated Miyoshi Nagamasa, who had been a loyal vassal of Harumoto, and backed his power on the military side in Enami, Settsu Province (the Battle of Eguchi).

He grew to be a daidaimyo (daimyo having a greater stipend) to govern, in total, nine provinces in the Kinki region (Settsu, Kawachi, Yamato, Tanba, Yamashiro, Izumi) and Shikoku (Awa, Sanuki, Awaji), as well as parts of Harima, Iyo, and Tosa provinces.

As he went up to Kyoto and declared his supreme power over Japan, he was called the first tenkabito [ja] and tried to establish the Miyoshi administration.

[6] Nagayoshi was a man of elegance and taste who loved renga (linked verse), favored Zen, and enjoyed reading classics such as The Tale of Genji.

He acted energetically and made achievements including developing the town of Sakai into a large trading port.

However, the resistance from the old power did not stop, and Hatakeyama Takamasa, one of the sankanrei (three families in the post of kanrei, or shogunal deputy), and Rokkaku Yoshikata, a hankoku shugo (military governor in charge of the half area of the province) and male cousin of Harumoto raised a rebellion against the Miyoshi.

With the successive deaths of Nagayoshi and his younger brothers and as the result of Hisahide and sanninshū bickering over the leadership, the Miyoshi clan declined.

Yasunaga was unaccounted for after the Honnō-ji Incident, and Masayasu died in the battle of Hetsu-gawa and had his rank of samurai and properties revoked.