Most sources agree that he took power in 1481 (the Aztec year "2 House"), succeeding his older brother Axayacatl. Although Tízoc's reign was relatively short, he began the rebuilding of the Great Pyramid of Tenochtitlan (a task completed by his younger brother Ahuitzotl in 1487), and also put down a rebellion of the Matlatzincan peoples of the Toluca Valley.
According to the Codex Mendoza, during Tizoc's reign the altepetl of Tonalimoquetzayan, Toxico, Ecatepec, Cillan, Tecaxic, Tolocan, Yancuitlan, Tlappan, Atezcahuacan, Mazatlan, Xochiyetla, Tamapachco, Ecatliquapechco, and Miquetlan were conquered.
Tizoc died in 1486, though it's still somewhat unclear how. Some sources suggest that he was poisoned, others that he was the victim of "sorcery" or illness. It has been suggested that either Tlacaelel or other members of the royal family (especially Ahuitzotl) were responsible for the poisoning of Tizoc.