In July 1934, while resting in the mountains of Nagano to recuperate from tuberculosis, he completed his first novel Onibi, which was published in 1935, although parts were immediately censored by the authorities.

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.

The scholar Mari Kotani called his 1939 story The Death's Head Stranger (髑髏検校, Dokuro-Kengyo) "the first successful adaptation of Bram Stoker's Dracula" and "the archetype of Japanese vampire literature.

In 2018 a literature professor found a previously missing piece of Yokomizo's wartime serial romance story "Yukiwariso," completing the manuscript for publication in book form.

The winner receives a statuette of Kosuke Kindaichi and a cash award of ¥10,000,000, making it one of the richest literary prizes in the world.