Yukawa graduated from Kyōto Imperial University (now Kyōto University) in 1929 and became a lecturer there; in 1933 he moved to Ōsaka Imperial University (now Ōsaka University), where he earned his doctorate in 1938. He rejoined Kyōto Imperial University as a professor of theoretical physics (1939–50), held faculty appointments at the Institute for Advanced Study in Princeton, New Jersey (U.S.), and at Columbia University in New York City, and became director of the Research Institute for Fundamental Physics in Kyōto (1953–70).

In 1935, while a lecturer at Ōsaka Imperial University, Yukawa proposed a new theory of nuclear forces in which he predicted the existence of mesons (meson), or particles that have masses between those of the electron and the proton. The discovery of one type of meson among cosmic rays by American physicists in 1937 suddenly established Yukawa's fame as the founder of meson theory, which later became an important part of nuclear and high-energy physics. After devoting himself to the development of meson theory, he started work in 1947 on a more comprehensive theory of elementary particles based on his idea of the so-called nonlocal field.