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In 1522, he fought the Amago clan along with his father, Yoshioki, to win the control of Aki Province. Upon Yoshioki's death in 1528, Yoshitaka became the head of Ōuchi clan. In the 1530s, he led a military actions in the northern Kyūshū, defeating Shoni clan to win control of the area. With his back then secure, in 1540 he again started combatting the Amago clan and by 1541, managed to completely control the Aki province.
However, in 1542, an invasion into Izumo Province ended in a disaster, with Yoshitaka losing his adopted son Ōuchi Harumochi along with large number of troops against Amago Haruhisa. He completely lost his ambitions of expanding his domains and devoted his energy to the arts and culture. His retainers split into two factions. Those led by Sagara Taketō wanted the Ōuchi clan to simply do nothing more than maintain the control of their current domains, while those led by Sue Harukata wanted to continue expanding. Yoshitaka chose former as his advisors and on 1551, the faction led by Sue Harukata revolted and attempted to take over the Ōuchi clan. With the control of troops in Harukata's hand, it was over in few days and Yoshitaka was forced to commit seppuku, after composing his death poem, which contained a quote from the Diamond Sutra:
Both the victor
and the vanquished are
but drops of dew,
but bolts of lightning –
thus should we view the world.
- Hall, John Whitney (1991). The Cambridge History of Japan, Volume 4. Cambridge University Press. p. 315. ISBN 9780521223553.
- Lidin, Olof G. (2002). Tanegashima - The Arrival of Europe in Japan. Taylor & Francis. p. 120. ISBN 9780203479575.
- "Death poems". The Samurai Archives. Retrieved 11 January 2014.