Joshua Lederberg was born in Montclair, New Jersey, and as he said in a 1998 interview, he must have been born a scientist. Lederberg showed an early aptitude and interest in science. In 1941, after high school, he entered Columbia University with the intention of studying medicine.

At Columbia, Lederberg became interested in Beadle and Tatum's Neurospora experiments, which opened up new and exciting research possibilities especially in the fledgling field of genetic analysis. In 1943, Lederberg got a job as a media-prep gopher in Frances Ryan's lab in the Department of Zoology. Ryan was a post-doc at Stanford in 1941-42, where he met Beadle and Tatum and became interested in using Neurospora as a research model. Ryan's mentorship and discussions with other faculty members and graduate students, "nourished [Lederberg's] education as a scientist." Lederberg found that scientific research was more intellectually challenging than the textbook drills of medical school.

From 1943-1944, Lederberg had a year of active duty in the United States Naval Reserves where he worked in a clinical parasitology laboratory at the U. S. Naval Hospital on Long Island, New York. He did not see active service, and although he was expected to return to medical school, at the end of 1944 Lederberg was back working in Ryan's lab.

1944 was the year Oswald Avery and his group published their paper on the transforming ability of DNA. Lederberg was profoundly influenced by the paper and its unlimited implications. He and Ryan immediately tried doing similar experiments using Neurospora. Unfortunately, they were unable to get the necessary mutants. Lederberg started to think about using a bacterial system even though there was still debate about whether bacteria had genes or not.

An opportunity came to test his ideas. Edward Tatum was moving from Stanford to Yale to start a new microbiology lab. Ryan encouraged Lederberg to apply to work in Tatum's lab and Lederberg was accepted in 1946. Tatum already had some E. coli mutants that were suitable for the kind of experiment Lederberg outlined. Within six weeks, Lederberg had the results he needed to prove bacterial conjugation occurred. For this work, Lederberg shared the 1958 Nobel Prize in Physiology or Medicine with Edward Tatum and George Beadle.

After obtaining a Ph.D. from Yale in 1948, Lederberg accepted a job at the University of Wisconsin. It was at Wisconsin that Lederberg developed the technique of bacterial replica plating in which bacterial colonies can be duplicated onto filters for further analysis. Lederberg also helped create and later served as the chair of the Department of Medical Genetics.

In 1958, Lederberg left Wisconsin for the Department of Genetics at Stanford University's School of Medicine. At Stanford, in addition to his own bacterial research, Lederberg had two other interests. One was artificial intelligence; Lederberg helped develop one of the first computer systems (DENDRAL) that could make decisions using a specific set of algorithms and a database. Lederberg's other interest was exobiology. He was an active consultant on the Space Science Board of the National Academy of Sciences, and was greatly interested in the Mariner and Viking missions as well as the search for extraterrestial life.

In 1978, he was appointed President of Rockefeller University - the site of Oswald Avery's Pneumococcus research. Since 1990, Lederberg has been Professor Emeritus of Rockefeller University. He serves on a number of government advisory boards and has written a weekly column Science and Man for the Washington Post where he informed the public on issues in science and research. Lederberg's latest project is to compile an informational web site at the National Library of Medicine using archival material he has accumulated over the years.