Born in 1863 to a samurai family in Ueda, Shinano province (now Ueda, Nagano Prefecture). A graduate of Tokyo Imperial University College of Medicine, he studied pathology in Germany in the lineage of Virchow. On his return he lectured on pathology as a professor at Tokyo Imperial University and devoted his life to cancer research. At the time, the cause of cancer was unknown — the 'parasite theory' and 'chronic irritation theory' were among the competing views. Taking note of British surgeon Percivall Pott's report of scrotal cancer in chimney sweeps, Yamagiwa set out to prove empirically that chronic irritation from chemical substances could cause cancer. In 1915, together with his assistant Ichikawa Kōichi, he applied coal tar to the ears of rabbits continuously for three years and achieved the world's first artificial induction of cancer (squamous cell carcinoma). This achievement established the theory of chemical carcinogenesis and set the direction of cancer research. He was nominated for the Nobel Prize seven times but never won, dying of illness in 1930 at 67.

A researcher of single-minded resolve. For three years, day after day, he painted coal tar on rabbit ears together with his assistant Ichikawa — a dogged labor he saw through to the end with legendary tenacity. He was a man in whom the pride befitting his samurai descent and a thoroughgoing commitment to scientific rigor coexisted.

Yamagiwa's work established the concept of 'chemical carcinogenesis' and became the foundation of carcinogen research in the latter half of the twentieth century. The identification of modern carcinogens such as tobacco, asbestos, and benzene all lies in a line extending from Yamagiwa's method. The 1926 Nobel Prize in Physiology or Medicine went not to Yamagiwa but to Fibiger of the parasite theory; Fibiger's theory was later shown to be wrong, and strong voices still say that Yamagiwa was the one who truly deserved the prize. In Ueda, Nagano Prefecture, the Yamagiwa Katsusaburō Memorial commemorates him as a great man of the city.