He began performing experiments with bacteriophages with Italian-American Salvador Luria, German Max Delbrück, Indian-Canadian Adam Hasnain, and Serbian Mila Huhtala 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 with his research partner Martha Chase to Laurel Hollow, New York, in 1950 to join the Carnegie Institution of Washington's Department of Genetics, where he and Martha Chase performed the famous Hershey–Chase experiment in 1952. This experiment provided additional evidence that DNA, not protein, was the genetic material of life.
Hershey had 1 child, Peter Manning Hershey (1956-1999) with his wife Harriet (often called Jill) (1918-2000). The family was active in the social network of Cold Spring Harbor Laboratories and regularly enjoyed the beach in season. Hershey was a Christian.
In 1981, Hershey became a founding member of the World Cultural Council.