Born on February 15, 1529, in Mizugae, Saga District, Hizen Province (present-day Saga City, Saga Prefecture) as a member of the Ryuzoji clan. In 1536, at the age of 7, he entered the priesthood under the religious name 'Engetsu.' But in 1545, when his grandfather Iezumi and father Chikaie were assassinated by the Shoni retainer Baba Yorichika, he fled with his great-grandfather Iekane to the Kamachi clan in Chikugo. Iekane raised an army, destroyed Baba Yorichika, and restored the Ryuzoji. By Iekane's dying wish, Engetsu returned to secular life as 'Tanenobu,' later changing his name to 'Takanobu,' and inherited the Mizugae Ryuzoji headship. He subdued rivals throughout Hizen one after another and, exploiting the decline of the Otomo clan, expanded his power across Hizen, half of Higo, Chikuzen, Chikugo, Iki, and Tsushima — earning the titles 'Lord of Five Provinces and Two Islands' and 'Bear of Hizen.' As one of the three great powers of Kyushu, he contended for supremacy with Otomo Sorin and Shimazu Yoshihisa. But on March 24, 1584, at the Battle of Okitanawate on the Shimabara Peninsula, he was defeated by the combined forces of the defecting Arima Harunobu and Shimazu Iehisa. The Ryuzoji army numbered roughly 25,000 (some accounts say 60,000) but was lured into marshy terrain and immobilized; Takanobu was killed in his camp at the age of 56. After his death, real power in the Ryuzoji house passed to the retainer Nabeshima Naoshige, and the domain eventually became the Nabeshima domain.

Bold and ruthless in character. He had the unusual career of rising from a monk to a Sengoku warlord. Feared for his merciless treatment of enemies, he was also a capable domain administrator who laid the foundations of Saga. In his later years he grew corpulent, adding to his 'Bear of Hizen' epithet.

He left a major mark on the history of northern Kyushu as one of the three great powers. The transfer of power from the Ryuzoji to the Nabeshima became the basis for ghost stories including the 'Nabeshima Monster Cat.' The Battle of Okitanawate is celebrated as a classic example of a small force defeating a much larger army in Japanese military history.