His works became the model for postwar Japanese mystery writing. He published many works via Kodansha's Weekly Shōnen Magazine in serialized form, concentrating only on popular mystery novels, based on the orthodox western detective story format, starting with 'Honjin Satsujin Jiken' (『本陣殺人事件』) and 'Chōchō Satsujin Jinken' (『蝶々殺人事件』) (both in 1946). However, soon after the end of World War II, his works received wide recognition and he developed an enormous fan following. The lack of Streptomycin and other antibiotics also meant that his tuberculosis could not be properly treated, and he joked with friends that it was a race to see whether he would die of disease or of starvation. However, during World War II, he faced difficulties in getting his works published due to the wartime conditions, and was in severe economic difficulties. Undeterred, Yokomizo followed on his early success with a second novel Ningyo Sashichi torimonocho (1938–1939).

In July 1934, while resting in the mountains of Nagano to recuperate from tuberculosis, he completed his first novel 'Onibi' (『鬼火』), which was published in 1935, although parts were immediately censored by the authorities. Yokomizo was attracted to the literary genre of historical fiction, especially that of the historical detective novel. After serving as editor in chief of several magazines, he resigned in 1932 to devote himself full-time to writing. However, drawn by his interest in literature, and the encouragement of Edogawa Rampo (江戸川乱歩), he went to Tokyo instead, where he was hired by the Hakubunkan publishing company in 1926. He graduated from Osaka Pharmaceutical College (currently part of Osaka University) with a degree in pharmacy, and initially intended to take over his family's drug store even though sceptical of the contemporary ahistorical attitude towards drugs.

He read detective stories as a boy and in 1921, while employed by the Daiichi Bank, published his first story in the popular magazine 'Shin Seinen' (新青年). Yokomizo was born in the city of Kobe, Hyōgo (兵庫県神戸市). Seishi Yokomizo ( 横溝正史) was a novelist in Shōwa period Japan.

The Inugami Curse by Seishi Yokomizo