Born in Edo as the eldest son of Tokugawa Hidetada, he was raised primarily by his wet nurse Kasuga no Tsubone because his mother O-e and father Hidetada doted on his younger brother Tadanaga. He became the third shogun in 1623 and pressed forward to establish the shogunate's authority. In 1635 he revised the Buke Shohatto to institutionalize the sankin-kotai (alternate attendance) system, establishing an important policy to curtail the power of outside daimyo. That same year he issued the seclusion edicts totally banning Japanese from traveling abroad and returning from overseas; in 1639 he prohibited Portuguese vessels from entering, completing the sakoku system. He suppressed the Christian uprising of the Shimabara Rebellion in 1637 and enforced the ban on Christianity thoroughly. He also actively confiscated and reassigned domains, driving the absolutization of shogunal power. He raised the prestige of the Tokugawa shogun to its apex as a "shogun by birth" and died in 1651 at age 48.

He saw himself as a "shogun by birth" and held an intense sense of authority and pride as a ruler. While he maintained deep trust and gratitude toward Kasuga no Tsubone throughout his life, he showed no mercy even toward his own flesh and blood when it came to preserving power, confining his brother Tadanaga and driving him to suicide. He also had a keen interest in the arts and practiced noh, tea ceremony, and calligraphy.

The institutionalization of sankin-kotai and the completion of the sakoku system determined the political and social structure of the Edo period for roughly 200 years thereafter. By strengthening control over the daimyo he absolutized shogunal power and established the position of the Tokugawa family as "shogun of all under heaven." The various institutions established under his governance became the skeleton of Japan's early modern state and exerted incalculable influence on later ages.