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Third son of the 9th regent Hojo Sadatoki, born in 1303. At his father's death in 1311 the 9-year-old Takatoki succeeded as head of the Tokuso (Hojo main) line, assisted by the family steward Nagasaki Enki. Appointed 14th regent in 1316 at age 14, he soon retreated from politics into legendary excesses chronicled in the Tsurezuregusa and Taiheiki: he summoned dengaku performers from Kyoto for nightly feasts, and kept thousands of fighting dogs gathered from across Japan — earning the mocking name 'Takatoki of the Dogs.' Real power lay with the steward Nagasaki Takasuke and his maternal grandfather Adachi Tokiaki, whose feud accelerated the regime's decay. In 1331, when Emperor Go-Daigo launched the Genko War to overthrow the shogunate, Takatoki — though formally retired after illness in 1326 — directed the response from his Tokuso position, exiling the emperor to Oki. But in 1333 the rebellions of Kusunoki Masashige, Akamatsu Enshin, the defection of Ashikaga Takauji (who took Rokuhara Tandai in Kyoto on May 7), and Nitta Yoshisada's uprising (Ikushina Shrine, May 8) overwhelmed the regime. On May 22, Nitta's army breached Inamuragasaki and assaulted Tosho-ji; Takatoki took his own life together with over 870 Hojo kin and retainers, age 31, ending the Kamakura shogunate after 150 years. The Hojo Takatoki Harakiri-yagura cave at the Tosho-ji ruins still preserves the memory.

Sickly and introverted, he indulged in dog-fighting and dengaku entertainment rather than statecraft. The Tsurezuregusa records his passion for fighting dogs and patronage of dengaku monks, while the Taiheiki paints him as a feeble ruler. Yet even after retiring he held fast to his Tokuso authority and led the resistance against Emperor Go-Daigo with determination — bearing alone the responsibility for the shogunate's fall.

The symbol of the Kamakura shogunate's 150-year end. His suicide extinguished the Hojo Tokuso line and broke the chain of warrior governments from Genji through Hojo, opening the way for the Kenmu Restoration and the Muromachi era. The 'Harakiri-yagura' cave at the Tosho-ji ruins in Kamakura remains a pilgrimage site. After generations of assassination, exile and suicide among the Kamakura lords, Takatoki's death marked the complete end of that tragic lineage.