Partly due to the successive premature deaths of their family heads, the power of the Mori clan was once weakened; however, when Motonari MORI (the 52nd) became the family head, he actively used his knowledge and strategies that enabled the clan to purge conflicts between families and tyrannical vassals and destroyed enemy forces, including the Takahashi clan of the Iwami Province, he further extended his power by taking over the powerful kokujin, Yoshikawa clan in the Aki Province and the Kobayakawa clan in the Bingo Province by the way of adoption.
毛利氏は当主の夭折が続いたこともあり、勢力は一時衰えたが、興元の弟である毛利元就（52代）が当主となると、元就はその知略を尽くし一族の反乱や横暴な家臣を粛清、石見国の高橋氏など敵対勢力を滅ぼし、さらに有力国人である安芸国の吉川氏と備後国の小早川氏を養子により乗っ取るなど、勢力を拡大。