The great-grandson of the last Incan leader Túpac Amaru, José Gabriel Condorcanqui was born in Tinta, in the province of Cusco, and received a Jesuit education at the San Francisco de Borja School. In 1760, he married Micaela Bastidas Puyucahua.
Condorcanqui inherited the caciqueship of Tungasuca and Pampamarca from his older brother, governing on behalf of the Spanish governor. But he sympathized with the plight of the native people and petitioned the Spanish government to improve conditions in the textile mills, the mines, and the villages. Unsuccessful, he adopted his great-grandfather's Incan name and a more native style of dress, and organized a rebellion, seizing and executing governor Antonio de Arriaga of Tinta in 1780.
Túpac Amaru II's rebellion was the first major uprising against the Spanish colonists in two centuries. It was suppressed after some successes like the Battle of Sangarará and he was soon captured. He was sentenced to witness the execution of his wife, his eldest son Hipólito, his uncle Francisco, his brother-in-law Antonio Bastidas, and some of his captains before his own death. He was sentenced to be tortured and put to death by dismemberment, in which four horses would have to tear apart each limb from his body, one limb tied to each horse. Unable to accomplish this execution, he was later drawn and quartered on the main plaza in Cuzco, in the same place his great-grandfather had been beheaded. When the revolt continued, the Spaniards executed the remainder of his family, except his 12-year-old son Fernando, who had been condemned to die with him, but was instead imprisoned in Spain for the rest of his life. It is not known if any members of the Inca royal family survived this final purge. At the same time, Incan clothing and cultural traditions, and self-identification as "Inca" were outlawed, along with other measures to convert the population to Spanish culture and government, until Peru's independence as a republic.