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Born in 1530 at Kasugayama Castle in Echigo Province as the fourth son of Nagao Tamekage, his childhood name was Torachiyo. He trained in scholarship and Zen at Rinsenji Temple in his youth, developing deep piety and both literary and martial accomplishments. In 1548 he received headship of the clan from his sickly brother Harukage, took the name Nagao Kagetora, and unified Echigo by suppressing rebellions one by one. When northern Shinano lords cried for help against Takeda Shingen's invasion, he marched in out of chivalric duty and fought five battles at Kawanakajima between 1553 and 1564. In 1561 he received the Kanto Kanrei (deputy shogun) title and the Uesugi surname from Yamanouchi Uesugi Norizane, adopting the name Uesugi Masatora (later Kenshin). A fervent devotee of Bishamonten, he fought under the single-character banner "Bi" and was celebrated as a "Warrior of Justice." Admired across Japan for fighting without selfish gain, he took up the defense of forces seeking his protection against the Hojo and Takeda alike. In the 1570s he extended his power through Hokuriku, bringing Kaga, Noto, and Etchu almost entirely under his control. In 1578, on the eve of a march on Kyoto to confront the Oda, he died suddenly at Kasugayama Castle at age 49 — one of the most formidable commanders of the era, undefeated to the end.

A scrupulously principled commander who placed justice and faith above all else. Driven by the ideal of fighting for righteousness rather than personal gain, he is famous for the legend of "sending salt to the enemy" — supplying salt to Takeda lands suffering from shortage. He took a lifelong vow of celibacy, styling himself an avatar of Bishamonten. His letters survive as highly valued historical documents.

"Sending salt to the enemy" endures as a celebrated story, conveying the importance of treating even adversaries with humanity. The Uesugi clan survived Kenshin's death as the Yonezawa Domain, leading eventually to the enlightened rule of Uesugi Yozan. His principled way of life deeply influenced later conceptions of bushido and still commands widespread admiration.