A devoted member of Nichiren Buddhism, Kiyomasa encouraged the building of Nichiren temples. He did not see eye-to-eye with Ishida Mitsunari, and Hideyoshi recalled him to Kyoto. He came into conflict with Konishi, who ruled the neighboring domain in Higo, and was a Christian. Kiyomasa was noted for brutally suppressing Christianity. At the battle of Hondo, he ordered his men to cut open the bellies of all pregnant Christian women and cut off their infant's heads.
During the Battle of Sekigahara, Kiyomasa remained in Kyûshû. Believing that the Toyotomi would fall without the help of the Tokugawa (and the hatred he had of Ishida Mitsunari commanding the Toyotomi forces), he sided with the eastern army of Tokugawa Ieyasu. For his loyalty to the Tokugawa, Kiyomasa was rewarded with the former territories of his rival Konishi (who had sided with Ishida), which when added to his existing territory, increased the Kumamoto domain to around 530,000 koku.
In his later years, Kiyomasa tried to work as a mediator for the increasingly complicated relationship between Tokugawa Ieyasu and Toyotomi Hideyori. In 1611, en route by sea to Kumamoto after one such meeting, he fell ill, and died shortly after his arrival. He was buried at Honmyô-ji temple in Kumamoto, but also has graves in Yamagata Prefecture and Tokyo. Kiyomasa is also enshrined in many Shinto shrines in Japan, including Katô Shrine in Kumamoto.
In 1910, Kiyomasa was posthumously promoted to junior 3rd court rank (jusanmi).