John Bell was born in Belfast, Northern Ireland. Both sides of his family were of Ulster Scots roots. When he was 11 years old, he decided to be a scientist, and at 16 graduated from Belfast Technical High School. Bell then attended the Queen's University of Belfast, and obtained a bachelor's degree in experimental physics in 1948, and one in mathematical physics a year later. He went on to complete a Ph.D. in physics at the University of Birmingham in 1956, specialising in nuclear physics and quantum field theory. In 1954, he married Mary Ross, also a Physicist, whom he had met while working on accelerator physics at Malvern, UK. Bell became a vegetarian in his teen years. According to his wife, Bell was an atheist.

In 1964, after a year's leave from CERN that he spent at Stanford University, the University of Wisconsin–Madison and Brandeis University, he wrote a paper entitled "On the Einstein-Podolsky-Rosen Paradox". In this work, he showed that carrying forward EPR's analysis permits one to derive the famous Bell's theorem. The resultant inequality, derived from certain assumptions, is violated by quantum theory.

But if he were to thoroughly explore the viability of Bohm's theory, Bell needed to answer the challenge of the so-called impossibility proofs against hidden variables. Bell addressed these in a paper entitled "On the Problem of Hidden Variables in Quantum Mechanics". (Bell had actually written this paper before his paper on the EPR paradox, but it did not appear until two years later, in 1966, due to publishing delays.) Here he showed that John von Neumann’s argument does not prove the impossibility of hidden variables, as it was widely claimed, due to its reliance on a physical assumption that is not valid for quantum mechanics—namely, that the probability-weighted average of the sum of observable quantities equals the sum of the average values of each of the separate observable quantities. Bell subsequently claimed, "The proof of von Neumann is not merely false but foolish!". In this same work, Bell showed that a stronger effort at such a proof (based upon Gleason's theorem) also fails to eliminate the hidden variables program. The supposed flaw in von Neumann's proof had been previously discovered by Grete Hermann in 1935, but did not become Common knowledge until after it was rediscovered by Bell.

In 1972 the first of many experiments that have shown (under the extrapolation to ideal detector efficiencies) a violation of Bell's inequality was conducted. Bell himself concludes from these experiments that "It now seems that the non-locality is deeply rooted in quantum mechanics itself and will persist in any completion." This, according to Bell, also implied that quantum theory is not locally causal and cannot be embedded into any locally causal theory. Bell regretted that results of the tests did not agree with the concept of local hidden variables:

Bell and his wife contributed substantially to the physics of particle accelerators and with numerous young theorists at CERN Bell developed particle physics itself. An overview of this work is available in the volume of collected works edited by Mary Bell, Kurt Gottfried and Martinus Veltman. Apart from his particle physics research Bell often raised an issue of special relativity comprehension and although there is only one written report on this topic titled "How to teach special relativity" available reprinted in this was a very important subject to him. Bell admired Einstein's contribution to special relativity, but warned in 1985 "Einstein's approach is ... pedagogically dangerous, in my opinion". In 1989 on the occasion of the centenary of the Lorentz-FitzGerald body contraction Bell writes "A great deal of nonsense has been written about the FitzGerald contraction". Bell preferred to think of Lorentz-FitzGerald contraction as a phenomenon that is real and observable as a property of a material body, which was also Einstein's opinion, but in Bell's view Einstein's approach leaves a lot of room for misinterpretation. This situation and the background of Bell's position is described in detail by his collaborator Johann Rafelski in the textbook "Relativity Matters" (2017). In order to combat misconceptions surrounding Lorentz-FitzGerald body contraction Bell adopted and promoted a relativistic thought experiment which became widely known as Bell's spaceship paradox.

Bell's career began with the UK Atomic Energy Research Establishment, near Harwell, Oxfordshire, known as AERE or Harwell Laboratory. After several years he moved to work for the European Organization for Nuclear Research (CERN, Conseil Européen pour la Recherche Nucléaire), in Geneva, Switzerland. There he worked almost exclusively on theoretical particle physics and on accelerator design, but found time to pursue a major avocation, investigating the foundations of quantum theory. He was elected a Foreign Honorary Member of the American Academy of Arts and Sciences in 1987. Also of significance during his career, Bell, together with John Bradbury Sykes, M. J. Kearsley, and W. H. Reid, translated several volumes of the ten-volume Course of Theoretical Physics of Lev Landau and Evgeny Lifshitz, making these works available to an English-speaking audience in translation, all of which remain in print.

Bell died unexpectedly of a cerebral hemorrhage in Geneva in 1990. It is widely claimed that unknown to Bell, that year he had been nominated for a Nobel Prize. His contribution to the issues raised by EPR was significant. Some regard him as having demonstrated the failure of local realism (local hidden variables). Bell's own interpretation is that locality itself met its demise.

In 2008, the John Stewart Bell Prize was created by the Centre for Quantum Information and Quantum Control at the University of Toronto. The prize is awarded every other year for significant contributions first published during the six preceding years. The award recognizes major advances relating to the foundations of quantum mechanics and to the applications of these principles. In 2009, the first award was presented by Alain Aspect to Nicolas Gisin for his theoretical and experimental work on foundations and applications of quantum physics — notably quantum nonlocality, quantum cryptography, and quantum teleportation.

However, in 2010, Jeffrey Bub published an argument that Bell (and, implicitly, Hermann) had misconstrued von Neumann's proof, claiming that it does not attempt to prove the absolute impossibility of hidden variables, and is actually not flawed, after all. (Thus, it was the physics community as a whole that had misinterpreted von Neumann's proof as applying universally.) Bub provides evidence that von Neumann understood the limits of his proof, but there is no record of von Neumann attempting to correct the near universal misinterpretation which lingered for over 30 years and exists to some extent to this day. Von Neumann's proof does not in fact apply to contextual hidden variables, as in Bohm's theory.

There is some disagreement regarding what Bell's inequality—in conjunction with the EPR analysis—can be said to imply. Bell held that not only local hidden variables, but any and all local theoretical explanations must conflict with the predictions of quantum theory: "It is known that with Bohm's Example of EPR correlations, involving particles with spin, there is an irreducible nonlocality." According to an alternative interpretation, not all local theories in general, but only local hidden variables theories (or "local realist" theories) have shown to be incompatible with the predictions of quantum theory.

Since 2015, there is also a street named Bell's Theorem Crescent in his city of birth, Belfast. At the event in memory of John Stuart Bell, a day was named after him, referring to the date he released Bell's Theorem, November 4.

In 2016, his colleague from CERN, Reinhold Bertlmann, wrote a lengthy piece "Bell's Universe: A Personal Recollection", explaining in some detail his amazement at finding out about Bell's paper on Bertlmann's socks, in which Bell compared the EPR paradox with socks.

Bell was impressed that in the formulation of David Bohm’s nonlocal hidden variable theory, no such boundary is needed, and it was this which sparked his interest in the field of research. Bell also criticized the standard formalism of quantum mechanics on the grounds of lack of physical precision: