Born in 1523, he inherited the headship of the Yamanouchi Uesugi clan and the office of Kanto Kanrei, making Hirai Castle in Kozuke his seat. At the night battle of Kawagoe in 1546 he was crushingly defeated by Hojo Ujiyasu, losing over 3,000 men and fleeing to Hirai Castle. Continued Hojo pressure led to Hirai Castle's fall in 1552, after which he fled to Echigo to rely on Nagao Kagetora, the future Uesugi Kenshin. In 1561, at Tsurugaoka Hachimangu in Kamakura, he transferred the Uesugi surname and the office of Kanto Kanrei to Kagetora, having him take the name Uesugi Masatora — the event that set in motion the emergence of "Uesugi Kenshin." In the Otate no Ran succession war that broke out after Kenshin's death in 1578, he sided with his adopted son Uesugi Kagetora, and was killed in battle at Otate on March 18, 1579, at age 57.

As head of the prestigious Yamanouchi Uesugi house he maintained his pride despite repeated military setbacks. Yet in choosing a successor, he recognized Kagetora (Kenshin)'s ability and entrusted him with the authority of Kanto Kanrei.

Though Hirai Castle itself fell into ruin, the succession of the Uesugi name and the Kanto Kanrei office from Norimasa to Kenshin became a pivotal turning point that reshaped the Sengoku-era history of the Kanto region.