Born in 1550 as the son of Kanki Yoriuji, lord of Kanki Castle. The Kanki family, a branch of the Akamatsu clan, held 10,000 koku in Kanki, Inami District, Harima Province (present-day Kako-cho, Kakogawa City, Hyogo). In 1578, during Hashiba Hideyoshi's invasion of Harima (the Miki Campaign), Yorisada sided with his overlord Bessho Nagaharu of Miki Castle and, reinforced by roughly 1,800 troops from the Bessho, held out at Kanki Castle. When the siege began on June 23, 1578, his roughly 2,000 defenders faced an Oda army of about 30,000 led by Oda Nobutada, Akechi Mitsuhide, Sakuma Nobumori, and Araki Murashige; an early clash at Omura-zaka is said to have ended in a defensive victory for Yorisada's side. However, Sakuma Nobumori is said to have persuaded Yorisada's uncle, Kanki Sadamitsu, to defect to the Oda side, and on July 16 of that year Yorisada died at age 28 as the castle fell — accounts differ as to whether he was assassinated in the betrayal or killed in the fighting.

He displayed enough military skill to repel the Oda forces in an early engagement, but is remembered as a tragic young castellan whose life was cut short by betrayal from within his own family.

The inner enclosure of Kanki Castle is now the site of Jorakuji Temple, and Yorisada's grave still stands in the cemetery behind its main hall. The site preserves the memory of the fierce fighting of the Miki Campaign and remains a place of local historical study.