The clan wielded significant power over the course of the Muromachi (1336–1467), Sengoku (1467–1600), and Edo periods, moving, however, from Shikoku, to Kinai, and then to Kyūshū over the centuries.

Over the course of this period, members of the Hosokawa clan were Constables (shugo) of Awa, Awaji, Bitchū, Izumi, Sanuki, Settsu, Tanba, Tosa, and Yamashiro Provinces.

This gave them the leverage to consolidate their power to some extent, and came to be strong rivals with the Ōuchi clan, both politically, and in terms of dominating trade with Ming China.

[4] The Hosokawa remained in Kyoto for roughly one hundred years, fleeing the city when it was attacked by lord Oda Nobunaga.

In 1787, the main family line descended from Tadatoshi became extinct with the death of the 7th lord, Shigekata's son Harutoshi (1758–1787; r. 1785–1787).

He was succeeded by his distant cousin Narishige, the sixth Lord of Udo (1755–c1835, r. 1787–1810) a direct descendant of Tadatoshi's younger brother Tatsutaka (1615–1645).

In 1810, Narishige abdicated his title in favor of his elder son Naritatsu (1788–1826, r. 1810–1826), who succeeded as the ninth lord of Kumamoto.

[9] Following the death of Narimori in 1860, his elder son Yoshikuni (1835–1876, r. 1860–1871) succeeded him as the eleventh and final ruling lord of Kumamoto.

Following the abolition of the feudal class in 1871, the Hosokawa clan and its branches were made part of the new nobility in the Meiji era.