The clan was also one of three families to dominate the post of Kanrei (Shogun's deputy), under the Ashikaga shogunate.
A conflict between Hosokawa Katsumoto, the fifth Kanrei, and his father-in-law Yamana Sōzen, over the shogunate's succession, sparked the Ōnin War, which led to the fall of the shogunate and a period of 150 years of chaos and war, known as the Sengoku period.