Having studied medicine in his native city of Turin, physics and radiology in Rome, and bacteriophage research techniques in Paris, Luria emigrated to America in 1940. There he met Max Delbrück and became associated with the American Phage Group, a body formed to study virus replication. He served as professor of microbiology at the Massachusetts Institute of Technology from 1950 to 1958, and in 1964 became Sedgwick Professor of Biology there.

Luria was interested in the way bacteria acquire resistance to virus infection and investigated whether this is due to an adaptive response or spontaneous mutation. His development of the fluctuation test, and its subsequent mathematical analysis by Delbrück, showed that resistance is indeed due to spontaneous mutation. The same year (1943) Luria also demonstrated mutation in bacteriophage; he completed his analysis of this phenomenon in 1951. He then worked on lysogeny, transduction, and host-controlled properties of viruses. For his contributions to the genetics of viruses and bacteria Luria shared the 1969 Nobel Prize for physiology or medicine with Delbrück and Alfred Hershey.