Gell-Mann was born in New York City, the son of Austrian immigrants. Having entered Yale at the age of fifteen, he went on to the Massachusetts Institute of Technology, where he completed his PhD in 1951. After spending a year at the Institute for Advanced Study, Princeton, and four years at the University of Chicago, Gell-Mann was appointed professor of physics in 1955 at the California Institute of Technology. In 1967 he was elected R. A. Millikan Professor of Theoretical Physics, a post he held until his retirement in 1993.

Gell-Mann was mainly concerned with the study of elementary particles. In the early 1950s physicists were puzzled by the ‘strange’ behavior of some apparently strongly interacting mesons. The kaons, as they were called, should have a lifetime of only 10^–23 second; they actually survived for some 10^–10 second. Gell-Mann suspected that some unknown property was conserved and that this explained the rapid decay of the kaons via the strong force. He named the new property ‘strangeness’ (S) and assigned the kaons a value S = +1. S was later defined as 2Q – B, or twice the charge minus the baryon number. Thus the proton with a charge of +½ and a baryon number of +1, will take the value S = 0, and this value will be conserved in all strong interactions. Similar ideas were proposed in 1954 by K. Nishijima in Japan.

New problems emerged. Physicists had become particularly worried by the discovery of large numbers of supposedly elementary particles. In the late 1950s it was possible to list and classify some thirty subatomic particles. Within five years another 70 ‘elementary’ particles had been discovered. The theorist's first priority was to bring some kind of order to this unwelcome abundance. In 1964, using group theory, and a number of conservation principles, Gell-Mann demonstrated that hadrons – i.e., particles such as baryons and mesons that interact strongly – could be classified into multiplets of 1, 8, 10, or 27 members. One such multiplet constructed with the group SU(3), or symmetry unity theory of dimension 3, yielded the octet. A similar proposal was made at the same time by the Israeli physicist Y. Ne'eman. The new synthesis was described in The Eightfold Way (1964), a work edited by Gell-Mann and Ne'eman. That there was more to their theory than arbitrary classifications was soon shown when the Ω^– (omega minus) particle, whose existence was previously unsuspected, was discovered in 1964 at Brookhaven with precisely the properties demanded for it by the SU(3) theory. The name itself alludes to the Buddhist path to enlightenment and to the eight quantum numbers required by the theory.

Following the discovery of the Ω^– Gell-Mann began to consider why the theory should be so successful in explaining hadron behavior. In his 1964 paper A Schematic Model of Baryons and Mesons, he proposed the existence of a more fundamental level of reality, that hadrons were composite, built out of more basic entities he proposed to call ‘quarks’. The name itself was taken from a phrase in James Joyce's Finnegans Wake – “three quarks for muster mark.” In Gell-Mann's original formulation he worked with three quarks, up (u), down (d), and strange (s), and three antiquarks (ū,d̄,s̄). As their most distinctive feature Gell-Mann assigned them fractional units of charge: s and d with a charge of –⅓, and u with +⅔. It was a simple matter to show that all baryons could be constructed with three quarks, and all mesons from a quark and an antiquark. Similar views were expressed in 1964 by G. Zweig.

The original model soon required some refashioning. A fourth quark property, ‘charm’, was proposed by Sheldon Glashow in 1970 and detected in 1974. This required extending the hadron classification scheme from a SU(3) group to a SU(4) group. Two further quarks have been added the t and b quarks, known variously as top and bottom, or ‘beauty’ and ‘truth’. The fifth b quark was identified by L. Lederman in 1977. The t quark, though occasionally glimpsed by optimistic experimentalists, was not firmly identified until 1995. A further complication of quark theory emerged with Nambu's proposal in 1965 that they came with three varieties of ‘color’.

In the 1980s Gell-Mann turned to the study of complexity. He was a cofounder in 1984 of the Santa Fe Institute which works on adaptive complex systems. Reportedly fluent in fifteen languages himself, Gell-Mann also worked in the field of historical linguistics.

For his numerous contributions to the study of elementary particles Gell-Mann was awarded the 1969 Nobel Prize for physics.