Amago Masahisa was the eldest son of Amago Tsunehisa, and designated heir of the clan.  As a sengoku daimyō and head of the Amago clan, Tsunehisa had established a major presence in the western provinces.  Like his father, Masahisa was known as a leader with a sharp mind, as well as a man of culture who enjoyed playing the flute.  Emperor Gotsuchi Mikado praised his literary knowledge.  Tsunehisa was able to unify Izumo under his control not only through his own prowess, but also through the contributions of Masahisa.  Masahisa received one of the characters in his name, as did his father, from the prior lord of the Amago, Kyōgoku Masatsune.

In 1518, Masahisa died in a nighttime attack on Ayo Castle in Izumo, also referred to as Togishi Castle.  He is said to have been struck in the throat by an arrow while standing atop a turret playing a flute to entertain the soldiers during a break in a prolonged battle.  The arrow was shot by Sakurai Sōteki, lord of Ayo Castle, from a bamboo forest across from Masahisa’s location.  After the incident, the Amago troops rallied and overcame the defenders.