Frisch and his aunt, Lise Meitner, gave the first scientific explanation of nuclear fission in 1939, and Frisch coined the term "fission."

After the Nazis took power in 1933, he left his research post in Hamburg. He continued his work in London and then in Copenhagen under Niels Bohr, where he became the first to detect the fragments of split uranium atoms.

• In 1940, he and Rudolf Peierls wrote the Frisch–Peierls memorandum, the first document to show that a compact atomic bomb could be made from a small amount of uranium-235. It became the basis of Britain's atomic bomb program and informed the Manhattan Project.

• At Los Alamos, he led the Critical Assemblies group, whose experiments determined how much enriched uranium the Hiroshima bomb required.