In the midst of this engagement in 1493, an incident known as the Meiō no seihen occurred, by which Hosokawa Masamoto, a kanrei, or deputy, held the shōgun, Ashikaga Yoshiki, in confinement.

Yoshioki withdrew his men from the battle to Hyōgo in Settsu Province to wait for the outcome of the event, which resulted in Yoshiki being deposed and replaced by Ashikaga Yoshizumi.

Nevertheless, Yoshioki's decision to withdraw his forces was well-received by the hikan, or administrators, in his birthplace of Kyōto, building relationships that benefit him later at the time of his succession to Masahiro.

Takemori himself had earlier taken over the clan after his father, Sue Hiromori, was assassinated in 1482 by Yoshimi Nobumori while attending a celebration at the Tsukiyama residence hosted by Masahiro.

In 1499, Sugi Takeakira, a senior retainer, colluded with a daimyō from Bungo Province named Ōtomo Chikaharu in an effort to seize control of the Ōuchi clan.

Upon learning of the plot, Yoshioki compelled Takeakira to commit seppuku, while Takahiro narrowly escaped to the protection of the Ōtomo clan in Bungo.

While en route, the boat that Masachika rode in came under distress, eventually reaching shore in the Ōuchi's main territory of Nagato Province.

During this turn of events, Hosokawa Masamoto operated behind the scenes, fearing the expansion of the Ōuchi influence and their connection to the deposed shōgun, Ashikaga Yoshitada (formerly under the name Yoshiki), who lived in exile in the northern provinces.

In the spring of 1497, Yoshioki's men defeated the Shōni in battles in front of the Shōfuku Temple in Hakata and at Takatorii Castle, forging onward to Hizen.

Upon returning to his hometown of Yamaguchi, Yoshioki paid a series of visits to local shrines, including Tamano-oya, Izumodai, Nikabe, Akada, and Asada.

This made Yoshioki an enemy of the Court, whereupon directives were sent out by Yoshitaka, the shōgun, and his bugyōnin to a total of twenty-eight daimyō and powerful kokujin in the western provinces.

In 1504, Yoshioki imposed a provisional tax in his territory to generate funds needed for his plans to march upon Kyōto under the pretext of reinstalling Ashikaga Yoshitada.

In 1507, Hosokawa Masamoto, the primary benefactor of Ashikaga Yoshizumi and chief governor of the bakufu, was assassinated as a result of an internal struggle for succession in the clan known as the Eishō sakuran.

Yoshioki took advantage of the situation by ordering daimyō from Kyūshū and the western provinces to mobilize for a march upon Kyōto to reinstall Yoshitada as the shōgun.

Pledging support for Yoshitane, Yoshioki entered the town of Sakai in Izumi Province and strengthened his ties to Hosokawa Takakuni in their mutual effort to pacify followers of Sumimoto in the Kinai Region.

Toward the end of 1508, the Tōdai Temple in Nara, requested return of the provincial governorate in Suō Province which had been under Ōuchi control since 1490, and closed their doors.

Takakuni ordered his retainer, Kawarabayashi Masayori, to construct the castle to serve as a forward operating base intended to thwart the advance of Sumimoto from Awa Province into the Kinai Region and, in particular, the capital of Kyōto.

Meanwhile, Takakuni ordered the mobilization of powerful kokujin from Settsu Province, including retainers of the Ikeda, Itami, Miyake, Ibaraki, Fukui, Ōta, Irie, and Takase clans.

Prior to retreating to Suō Province, Yoshioki ordered Tagaya Takeshige to firmly protect Sakai, which had the additional consequence of blocking the passage of forces from Shikoku to support Sumimoto.

In 1516, the shōgun and his bugyō, or administrators, issued declarations granting perpetual, exclusive rights to the Ōuchi clan to manage trade with the Ming Dynasty of China.

Much to the disdain of Hosokawa Takakuni, an exclusive grant of rights to the Ōuchi meant that Hakata would become the center of trade with China, resulting in a significant loss of revenue.

Gradually, Ashikaga Yoshitane (having changed his name from Yoshitada following his return as shōgun) had a falling out with Takakuni, while kokujin from Iwami and Aki provinces who could no longer endure their extended stays in Kyōto began to depart on their own accord.

Nevertheless, unable to halt the expanding influence of the Amago, in 1518, Yoshioki resigned his official post as kanreidai and left Sakai to return to Yamaguchi.

Yamana Nobutoyo, shugo of Bingo Province, lost control after enduring attacks from Tsunehisa from the north and Sue Okifusa from the west under orders from Yoshioki.