The Oûchi family had joined Ashikaga Takauji in 1336, and for their efforts in the war against the Ashikaga's opponents were named shugo of Suo and Nagato in 1363. Yoshihiro was the son of Oûchi Hiroyo and assisted Imagawa Sadayo in his Kyushu campaign. His father died in 1579 and he became involved in a power struggle with his brother, whom he defeated at Sakariyama in 1380. In 1591 Yoshihiro led an army in the name of shogun Ashikaga Yoshimitsu into the capital region and fought with Southern Court adherents there. Yoshimitsu rewarded his services with a further two provinces. Yoshihiro's greatest contribution to the Ashikaga came in 1392, when he managed to convince the Southern Court Emperor to surrender, thus bringing the Nambuchuko Period effectively to a close. Ironically, Oûchi was to rise in revolt against the Bakufu as a result of what he considered unfair demands (the shôgun requested that he build him a villa at Kitayama, for instance) on his resources. To this end, he had carefully made arrangements for support among various other shugo, and then withdrew his forces from Kyoto to the city of Sakai. Yoshimitsu initially attempted to solve the crisis peacefully, but finding Yoshihiro determined to fight, elected to make the first move. He gathered an army composed of the Hatakeyama, Hosokawa, and Shiba and made a general advance on Sakai by land while at the same negotiating with the Inland Sea pirates (whose support Yoshihiro had been counting on) to affect a naval blockade. Yoshihiro's rebellion quickly began to come undone, in part due to Yoshimitsu's prompt response and also due to a good deal of promised support from the Kanrei Ashikaga Mitsukane and others failing to materialize. At the same time, Yoshihiro's Iwami and Izumi troops proved incompletely unreliable. Oûchi resistance was nonetheless stubborn, but in the 12th month of 1399 Bakufu troops managed to set fire to the city. Amid an all-out assault by Yoshimitsu's forces, Yoshihiro commited suicide.

Apart from his military activities, Yoshihiro was active in the trade with China and worked towards securing Oûchi dominance in this area

Compiled by F.W. Seal