Amago Sanehisa was a family member of the Amago clan and the eldest son of Amago Kunihisa. Similar to his father, Sanehisa carried a reputation as a fierce warrior demonstrated by his military exploits as a member of the elite force known as the shingūtō.  After his uncle, Enya Okihisa, died in a failed rebellion, Amago Tsunehisa, Sanehisa’s grandfather and head of the Amago clan, banished and reduced the landholdings of the kokujin and others who supported the rebellion.  Sanehisa’s father, Kunihisa, inherited the former territories of the Enya, while Sanehisa joined the allied Taga clan, a kokujin, through marriage.  As a consequence, Kunihisa and his family acquired control of western Izumo.  This outcome created a dependency by Amago Haruhisa, head of the clan, on Kunihisa to manage political and military affairs in western Izumo, conflicting with Haruhisa’s aim to govern all of Izumo Province. Displays of arrogance based on their military exploits further raised tensions between Haruhisa and senior retainers of the Amago clan on the one hand and Kunihisa, Sanehisa, and the shingūtō forces on the other.

Sanehisa, together with a senior retainer named Ushio Yoshikiyo, lord of Ushio Castle, governed Mimasaka.  In 1554, Haruhisa purged Sanehisa and his father, Kunihisa, along with most of the shingūtō.  According to one account, Haruhisa ordered the assassination of Sanehisa by elders in the Amago clan named Ōnishi Jūbei and Tachibana Yukitsuna, or, he may have taken his own life in the shingūtō quarters.  Sanehisa’s fifth son escaped to Kyōto with the help of retainers and joined a temple, later exiting life as a monk to return as Amago Katsuhisa.