Nagao Masakage was the son of Nagao Fusanaga, heir to the Ueda-Nagao Clan, and master of Sakato Castle in Echigo. He was betrothed to his distant relative Nagao Kagetora (later Uesugi Kenshin)'s older sister Sentouin in 1537. He retired from the position of clan head in 1548 in favor of Kagetora.

Masakage rebelled against Kagetora in 1550, but surrendered to his fierce attacks in 1551 and thereafter became one of his chief vassals. In 1556, he managed to persuade Kagetora to come back to the clan when he decided to give up the title of clan head and become a monk.

Masakage died of drowning in 1564 in a pond near Sakato Castle. Some say that he fell off a boat while drunk, though Kenshin maintained that it was assassination.

His son Uesugi Kagekatsu inherited the position of Nagao clan head, but since he had been adopted by Kenshin, the Ueda branch of the Nagao family merged with the Fuchuu branch.