Gerald Edelman was born in 1929 in Ozone Park, Queens, New York, to Jewish parents, physician Edward Edelman, and Anna (née Freedman) Edelman, who worked in the insurance industry. He studied violin for years, but eventually realized that he did not have the inner drive needed to pursue a career as a concert Violinist, and decided to go into medical research instead. He attended public schools in New York, graduating from John Adams High School, and going on to college in Pennsylvania where he graduated magna cum laude with a B.S. from Ursinus College in 1950 and received an M.D. from the University of Pennsylvania School of Medicine in 1954.

Edelman married Maxine M. Morrison in 1950. They have two sons, Eric, a visual Artist in New York City, and David, an adjunct professor of neuroscience at University of San Diego. Their daughter, Judith Edelman, is a bluegrass musician, recording Artist, and Writer. Some observers have noted that a character in Richard Powers' The Echo Maker may be a nod at Edelman.

After a year at the Johnson Foundation for Medical Physics, Edelman became a resident at the Massachusetts General Hospital; he then practiced Medicine in France while serving with US Army Medical Corps. In 1957, Edelman joined the Rockefeller Institute for Medical Research as a graduate fellow, working in the laboratory of Henry Kunkel and receiving a Ph.D. in 1960. The institute made him the Assistant (later Associate) Dean of Graduate Studies; he became a professor at the school in 1966. In 1992, he moved to California and became a professor of neurobiology at The Scripps Research Institute.

While in Paris serving in the Army, Edelman read a book that sparked his interest in antibodies. He decided that, since the book said so little about antibodies, he would investigate them further upon returning to the United States, which led him to study physical chemistry for his 1960 Ph.D. Research by Edelman and his colleagues and Rodney Robert Porter in the early 1960s produced fundamental breakthroughs in the understanding of the antibody's chemical structure, opening a door for further study. For this work, Edelman and Porter shared the Nobel Prize in Physiology or Medicine in 1972.

Edelman and his colleagues used cyanogen bromide and proteases to fragment the antibody protein subunits into smaller pieces that could be analyzed for determination of their amino acid sequence. At the time when the first complete antibody sequence was determined (1969) it was the largest complete protein sequence that had ever been determined. The availability of amino acid sequences of antibody proteins allowed recognition of the fact that the body can produce many different antibody proteins with similar antibody constant regions and divergent antibody variable regions.

In its Nobel Prize press release in 1972, the Karolinska Institutet lauded Edelman and Porter's work as a major breakthrough:

The first of Edelman's technical books, The Mindful Brain (1978), develops his theory of Neural Darwinism, which is built around the idea of plasticity in the neural network in response to the environment. The second book, Topobiology (1988), proposes a theory of how the original neuronal network of a newborn's brain is established during development of the embryo. The Remembered Present (1990) contains an extended exposition of his theory of consciousness.

Topobiology is Edelman's theory which asserts that morphogenesis is driven by differential adhesive interactions among heterogeneous cell populations and it explains how a single cell can give rise to a complex multi-cellular organism. As proposed by Edelman in 1988, topobiology is the process that sculpts and maintains differentiated tissues and is acquired by the energetically favored segregation of cells through heterologous cellular interactions.

In his later career, Edelman was noted for his theory of consciousness, documented in a trilogy of technical books and in several subsequent books written for a general audience, including Bright Air, Brilliant Fire (1992), A Universe of Consciousness (2001, with Giulio Tononi), Wider than the Sky (2004) and Second Nature: Brain Science and Human Knowledge (2007).

Edelman founded and directed The Neurosciences Institute, a nonprofit research center in San Diego that between 1993 and 2012 studied the biological bases of higher brain function in humans. He served on the scientific board of the World Knowledge Dialogue project.

Later in his life, he had prostate cancer and Parkinson's disease. Edelman died on May 17, 2014 in La Jolla, California, aged 84.