He was born to Hojo Tokiuji and a daughter of Adachi Kagemori. He became shikken after his brother Tsunetoki's death. Immediately after the succession, he crushed a coup plot by former shogun Kujo Yoritsune and Tokiyori's relative Nagoe Mitsutoki. In the next year, he let Adachi Kagemori destroy the powerful Miura clan in the Battle of Hochi. He recalled his experienced grandfather's brother Hojo Shigetoki from Kyoto and appointed him as rensho. In 1252 he replaced shogun Kujo Yoritsugu with Prince Munetaka. He successfully solidified the power base.
He has been praised for his good administration. He worked on reforms mainly by puting various regulations. He reduced service of the vassals to guard Kyoto. He worked toward resolving increasing land disputes of his vassals. In 1249 he set up the legal system of Hikitsuke or High Court.
In 1252 he started to make policies at private meetings held at his residence instead of instead of discussing at Hyōjō (評定), the council of the shogunate. In 1256 when he became a Buddhist priest, he transferred the position of shikken to Hojo Nagatoki, a son of Shigetoki while Tokiyori's infant son Tokimune succeeded tokuso, the head of the Hojo clan. Tokiyori continued to rule in fact without any official posotion. This is considered the begining of the tokuso dictatorship.
There ramain various legends that Tokiyori traveled incognito throughout Japan to inspect actual conditions and relieve people. He died in 1263.