Delbrück received a Ph.D. in physics (1930) from the University of Göttingen. His interest in bacteriophages was aroused while he was a research assistant at the Kaiser Wilhelm Institute for Chemistry in Berlin (1932–37). A refugee from Nazi Germany, Delbrück went to the United States in 1937, serving as a faculty member of the California Institute of Technology (1937–39; 1947–81) and of Vanderbilt University (1940–47). He became a U.S. citizen in 1945.

In 1939 Delbrück discovered a one-step process for growing bacteriophages that, after a one-hour latent period, would multiply to produce several hundred thousands of progeny. Delbrück soon began to collaborate with Luria, and in 1943 they announced their discovery that a bacterium that has been infected by a bacteriophage can undergo spontaneous mutations so that it becomes immune to the phage. In 1946 Delbrück and Hershey independently discovered that the genetic material of different kinds of viruses can combine to create new types of viruses. This process was previously believed to be limited to higher, sexually reproducing forms of life.