From this line, Sasaki Takauji made a success at the Muromachi shogunate and the Amago clan originated from his brother.
New to the ranks of the daimyo were the Asakura, Amago, Nagao, Miyoshi, Chōsokabe, Hatano, and Oda.
However, after the Ōnin War, the Amago clan expanded power based in Gassantoda Castle and the Masuda clan dominated Iwami Province.
The Iwami Ginzan Silver Mine was located between Amago territory and Masuda territory, so there were many battles between these clans for the silver.
Sandwiched between the powerful Amago and Ōuchi clans, Motonari led the clan by carefully balancing actions and diplomacy.
It is said he escaped by night with some other kids from the castle of his father, and met lord Amago Tsunehisa and his troops.
In 1518 Amago Tsunehisa made a series of raids into the Ōuchi clan's lands, falling back with the return of Ōuchi Yoshioki from Kyōto. In 1521 a formal peace treaty was signed between the two clans but this lasted for but one year.
In 1522, Tsunehisa marched into Aki Province, forcing Motonari, whose lands sat directly in the Amago's path, to submit.
After the battle Motonari insisted on saving Naonobu but Amago Tsunehisa executed him for his shameful and disloyal act.
Along with the family troubles concerning succession, Motonari and Amago Tsunehisa gradually grew hostile towards one another.
In June, Yoshioki sent their army to Kagamiyama Castle and took it from the Amago clan.
Amago Tsunehisa began making dealings with Takahashi Okimitsu (高橋興光), a maternal relative of the late Mōri Kōmatsumaru who had earlier schemed to place Motonari's brother, Aiō Mototsuna, as head of the Mōri clan.
By the end of the decade the Ōuchi and Amago families began to see the Mori with new respect and suspicion.
The Amago clearly would not have any faith in Motonari as he had betrayed them and defeated their allies.
In the same year, Sato-Kanayama Castle (佐東銀山城) owned by the Takeda clan on the Amago side fell to the Ōuchi clan despite reinforcements from the Amago clan.
The family head Takeda Nobuzane (武田信実) escaped to Wakasa (若狭) where the Takeda had a branch family and later took refuge with the Amago clan.
Motonari successfully defended an attack by Amago Haruhisa on his castle in the 1540–41 Siege of Koriyama.
Amago Haruhisa conceived of a plan to destroy Mōri Motonari and bring Aki province under the sway of the Amago.
When a council of the Amago retainers was called to discuss the planned campaign, almost all spoke in favor of the attack.
Amago Hisayuki, however, considered the risks to be too great and spoke out against it, but was derided by Amago Tsunehisa as a coward and publicly humiliated.