Born in 1566 as the eldest son of Sanada Masayuki. His younger brother was Sanada Nobushige (Yukimura). He married Komatsu-dono, daughter of Honda Tadakatsu and adopted daughter of Ieyasu, forging a bond with the Tokugawa. At Sekigahara in 1600, while his father and brother sided with the Western Army, Nobuyuki chose the Tokugawa side—a decision made at the famous 'Parting at Inubushi,' which ensured the Sanada would survive regardless of who won. After the war he held Ueda at 30,000 koku, then was transferred to Matsushiro at 100,000 koku in 1622, establishing the Sanada as a lasting daimyo house. He retired in 1656 and died on October 17, 1658, at the remarkable age of 93.

Calm, composed, and pragmatic. In contrast to his brother Yukimura's flamboyance, he was understated but steadfast, always putting the survival of the clan first. His endurance was reflected in his extraordinary longevity.

While his brother Yukimura died gloriously as 'the greatest warrior in Japan,' Nobuyuki preserved the Sanada house and established it as a modern daimyo family. The Matsushiro domain lasted until the Bakumatsu, producing figures like Sakuma Shozan. His extraordinary lifespan of 93 years is legendary among Sengoku warriors.