Yoshiharu Horio was initiated into the Oda in in 1560 after he wrestled a wild boar, and became a staff officer under Hideyoshi Hashiba. He fought in the Battle of Mt. Inaba Castle in 1567 and the Battle of Takamatsu Castle in 1582, in which he slew Mori retainer Muneharu Shimizu. After the death of Nobunaga Oda, he fought under Hideyoshi Hashiba's Toyotomi clan at the Battle of Yamazaki, in which he killed Toshikazu Saito, and later at the Siege of Odawara in 1590.
He was awarded territory in Bitchu Province, where the Matsue clan resided in Takamatsu Castle. In 1598, after the death of Hideyoshi, his clan sided with the Anti-Ishida Coalition of Masanori Fukushima, an alliance of Hideoyshi's former vassals who resisted Mitsunari Ishida's seizure of power as de facto Shogun. Horio was wounded by Yukimura Sanada, who defended the keeps from the Fukushima loyalists. Afterwards, he joined Ieyasu Tokugawa in his campaign against Ishida, and fought at the Battle of Sekigahara in 1600, where the Tokugawa destroyed the Western Army and took over Japan.