Yoshihisa Shimazu assumed leadership as the sixteenth head of the Shimazu clan in 1566, following his father Takahisa. Driven to unify Kyushu, he relied on his brothers Yoshihiro, Toshihisa, and Iehisa, alongside retainers Tadamune Ijuin and Tadamoto Niiro. His campaigns first solidified control over Satsuma and Ōsumi provinces before advancing into Hyūga, where he crushed the Itō clan through victories at Kizakihara (1572), Takabaru (1576), and Kamiya (1578).

At the Battle of Mimigawa in 1578, his brothers’ strategic flanking maneuvers secured a decisive triumph against the Ōtomo clan. He later targeted the Ryūzōji clan in Higo, culminating in the 1584 Battle of Okinawate where his forces killed daimyō Takanobu.

When Toyotomi Hideyoshi invaded Kyushu in 1587, Yoshihisa surrendered after initial defiance. To avoid execution, he shaved his head, took the monastic name Ryūhaku, and transferred formal clan leadership to Yoshihiro due to lacking a male heir. Despite retiring, he maintained substantial influence.

In 1600, ahead of the Battle of Sekigahara, he withheld reinforcements from Yoshihiro—who fought for the Western Army—reflecting his aversion to involving the clan in central conflicts and straining their bond. A documented post-Sekigahara conversation with Tokugawa Ieyasu underscored his leadership philosophy: he credited past successes to delegating authority to skilled subordinates like his brothers and retainers while remaining at Kagoshima Castle.

He spent his final years in relative seclusion until dying of illness in 1611.