He was born in Owosso, Michigan and received his B.S. in chemistry at Michigan State University in 1930 and his Ph.D. in bacteriology in 1934, taking a position shortly thereafter at the Department of Bacteriology at Washington University in St. Louis.
He began performing experiments with bacteriophages with Italian-American Salvador Luria and German Max Delbrück in 1940, and observed that when two different strains of bacteriophage have infected the same bacteria, the two viruses may exchange genetic information.
He moved to Cold Spring Harbor, New York, in 1950 to join the Carnegie Institution of Washington's Department of Genetics, where he performed the famous Hershey-Chase blender experiment with Martha Chase in 1952. This experiment provided additional evidence that DNA, not protein, was the genetic material.
He became director of the Carnegie Institution in 1962 and was awarded the Nobel Prize in Physiology or Medicine in 1969, shared with Luria and Delbrück for their discovery on the replication of viruses and their genetic structure.
Hershey had one son, Peter, with his wife Harriet.
After Hershey died, another phage worker, Frank Stahl, wrote: "The Phage Church, as we were sometimes called, was led by the Trinity of Delbrück, Luria, and Hershey. Delbrück's status as founder and his ex cathedra manner made him the pope, of course, and Luria was the hard-working, socially sensitive priest-confessor. And Al (Hershey) was the saint."
- Nobel biography
- Biographical Memoir: Alfred Day Hershey by Franklin W. Stahl for the National Academy of Sciences