Ôtani Yoshitsugu's origins are unclear, however one theory holds that Yoshitsugu's family were former retainers of the Ôtomo family of Bungo province. He was recommended to Toyotomi Hideyoshi (possibly by the young Ishida Mitsunari) around 1574 and quickly rose through the ranks. He attacked Takigawa Kazumasu in the 1583 Shizugatake campaign and afterwards, following Hideyoshi's defeat of Shibata Katsuie, was given Tsuruga in Echizen province. He assisted in the logistical aspects of Hideyoshi's 1587 invasion of Kyushu and was present for the Siege of Odawara Castle in 1590. He was later dispatched to the northern provinces as a land survey officer, though his activities during the 1590's are otherwise obscure, possibly due to a worsening case of leprosy he was suffering from by this point. While in the north he was forced to deal with the resistance of Onodera Yasumichi in 1599, whose castle of Ômori Yoshitsugu besieged. In 1600 he at first thought of joining Tokugawa Ieyasu's side in the coming war but was convinced by Ishida Mitsunari to follow the latter instead. Though suffering from now-advanced leprosy, he joined the 'western' forces on the battlefield at Sekigahara and directed his troops from within a palanquin. After the defection of Kobayakawa Hideaki to Tokugawa Ieyasu's side, he ordered a retainer to cut off his head and spirit it away. His daughter was married to Sanada Yukimura.