Born in 1533 as the eldest son of Shimazu Takahisa, Yoshihisa was known as the first of the celebrated 'Four Brothers' alongside Yoshihiro, Toshihisa, and Iehisa, and succeeded as the 17th head of the Shimazu clan. After crushing Otomo Yoshimune (son of Otomo Sorin) at the Battle of Mimikawa in 1578, he continued expanding Shimazu power and came close to unifying Kyushu. In 1587, however, he could not withstand the massive invasion force led by Toyotomi Hideyoshi and surrendered, his domain reduced to Satsuma and Osumi provinces alone. He then took Buddhist vows and passed clan leadership to his nephew Tadatsune (son of Iehisa), devoting himself to internal governance and working to secure the Shimazu family's survival and the foundations of the Satsuma domain. In 1604 he built Kokubu Castle (Maizuru Castle) in Osumi's Kokubu and moved there in retirement, retaining great influence within the clan even after stepping down. He died at this castle on January 21, 1611, at age 79.

As eldest of the Four Brothers, he possessed strong leadership in uniting the clan, guiding it to victory in battles such as Mimikawa. After his surrender to Hideyoshi, he pragmatically shifted his focus to internal governance, showing calm judgment that prioritized the survival of his house above all else.

Though often overshadowed by his brother Yoshihiro's martial fame, Yoshihisa played a crucial role as the leader who built the Shimazu clan's peak expansion toward Kyushu unification and, after the surrender to Hideyoshi, guided the family's survival as its head. The ruins of Kokubu Castle, where he spent his final years, remain a historic site in present-day Kirishima City.