Born 1922 in Berlin, he grew up in Vienna before emigrating in 1938. He received an electrical engineering certificate from the School of Technology, City of Oxford (now Oxford Brookes University) and then Wesleyan University, where he received B.A. (1941) and M.A. (1942) degrees.
As a student of Percy Williams Bridgman, he obtained his Ph.D. at Harvard in 1948. His chief interests are in the history and philosophy of science, in the physics of matter at high pressure, and in the study of career paths of young scientists. Along with co-author Gerhard Sonnert he has studied and published works on the gender gap in science studies and careers. In 1952, he published Introduction to Concepts and Theories in Physical Sciences, a seminal work in the development of physics education, which led to Harvard Project Physics, the NSF sponsored national curriculum-development project that he co-directed. 
Gerald Holton is a Fellow of the American Physical Society, the American Philosophical Society, and the American Academy of Arts and Sciences (1956), as well as several European learned societies. He served as President of the History of Science Society from 1983-84 and served on a number of U.S. National Commissions, including those on UNESCO and Excellence on Education. He also served on the board of trustees of Science Service, now known as Society for Science & the Public, from 1972-1978.
His book publications include Thematic Origins of Scientific Thought, The Scientific Imagination, Einstein, History and Other Passions, Science and Antiscience, and Victory and Vexation in Science. He is also author, with Gerhard Sonnert, of What Happened to the Children Who Fled from Nazi Persecution.
Holton is founding editor of the quarterly journal Daedalus, and founder in 1972 of the Newsletter on Science, Technology, and Human Values (from 1976 Science, Technology, and Human Values). He was also on the editorial committee of the Collected Papers of Albert Einstein. Professor Holton has received the Sarton Medal of the History of Science Society, the Andrew Gemant Award of the American Institute of Physics, the Abraham Pais Prize of the American Physical Society, and the Robert A. Millikan award of the American Association of Physics Teachers.
In 1981 the National Endowment for the Humanities selected Holton for the tenth Jefferson Lecture, the U.S. federal government's highest honor for achievement in the humanities. Holton was the first scientist selected for this honor, and his lecture was entitled "Where is Science Taking Us?" In his lecture, Holton argued that Jefferson's vision of science as a force for social improvement was still viable, opined that there had been a "relocation of the center of gravity" of scientific inquiry toward solving society's important problems, and cautioned that science education had to be improved dramatically or only a small "technological elite" would be equipped to take part in self-government.
A considerable and growing collection of his papers are being collected by Harvard University Archives, donated by Holton since 2007. One document box is entitled "Strange melodies" and "crackpot letters", 1953-1980.
- Holton, Gerald J. "United States Public Records Inde". familysearch. Retrieved 11 December 2013.
- "Gerald James Holton personal archive, 1919-2011, 2013 and undated-an inventory". Harvard University Archives. President and Fellows of Harvard College. Retrieved 7 September 2013.
- "Gerald Holton Wins Pais Prize", History of Physics Newsletter, American Physical Society, Spring 2008.
- "Book of Members, 1780–2010: Chapter H". American Academy of Arts and Sciences. Retrieved August 5, 2014.
- The History of Science Society "The Society: Past Presidents of the History of Science Society", accessed 4 December 2013
- Jefferson Lecturers at NEH Website (accessed January 22, 2009).
- Alvin Krebs and Robert McG. Thomas, "Notes on People; Jeffersonian Theory Gets New Lease on Life," New York Times, May 12, 1981.
- "Holton, in Jefferson Lecture, Criticizes Science Education," Harvard Crimson, May 15, 1981.