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Eldredge began his undergraduate studies in Latin at Columbia University. Before completing his degree he switched to the study of geology under Norman D. Newell. It was at this time that his work at the American Museum of Natural History began, under the combined Columbia University-American Museum graduate studies program.
In 1969, Eldredge became a curator in the Department of Invertebrates at the American Museum of Natural History, and subsequently a curator in the Invertebrate Paleontology section, a position from which he recently retired. He was also an Adjunct Professor at the City University of New York. His specialty was the evolution of mid-Paleozoic Phacopida trilobites, a group of extinct arthropods that lived between 543 and 245 million years ago.
Eldredge and Stephen Jay Gould proposed punctuated equilibria in 1972. Punctuated equilibrium is a refinement to evolutionary theory. It describes patterns of descent taking place in "fits and starts" separated by long periods of stability.
Eldredge went on to develop a hierarchical vision of evolutionary and ecological systems. Around this time, he became focused on the rapid destruction of many of the world's habitats and species. In his book Unfinished Synthesis (1985), he proposed an extended evolutionary synthesis.
Throughout his career, he has used repeated patterns in the history of life to refine ideas on how the evolutionary process actually works. Eldredge is proponent of the importance of environment in explaining the patterns in evolution.
He has published more than 160 scientific articles, books, and reviews, including Reinventing Darwin, an examination of current controversies in evolutionary biology, and Dominion, a consideration of the ecological and evolutionary past, present, and future of Homo sapiens.
With J. Cracraft (eds.) 1979. Phylogenetic Analysis and Palaeontology. Columbia University Press, New York
With J. Cracraft. 1980. Phylogenetic Patterns and the Evolutionary Process. Method and Theory in Comparative Biology. Columbia University Press, New York, 349 p. Japanese edition, Soju Shobo, 1990
1982. The Monkey Business: A Scientist Looks at Creationism. Pocket Books, New York. 157 p. Japanese edition, 1992
With I. Tattersall. 1982. The Myths of Human Evolution. Columbia University Press, New York. 197 p. Japanese edition arranged through Columbia U. Press.; Spanish edition 1986: Fondo de Cultura Economica, Mexico; Portuguese ed.: 1984, Zahar Editores, Rio de Janeiro; Italian ed., 1984: Boringheri
With S. M. Stanley (eds.). 1984. Living Fossils. Springer Verlag, New York.
1985. Time Frames. Simon and Schuster, New York. 240 pp. Great Britain: Heilman; Princeton University reprint edition. Italian edition, 1991, hopefulmonster editore
1985. Unfinished Synthesis: Biological Hierarchies and Modern Evolutionary Thought. Oxford University Press, New York
1987. Life Pulse: Episodes in the History of Life. Facts on File, New York. Pelican edition (Great Britain)
(ed.). 1987. Natural History Reader on Evolution. Columbia University Press, New York
1989. Macroevolutionary Dynamics: Species, Niches and Adaptive Peaks. McGraw Hill, New York. Japanese edition: McGraw Hill Publishing Co., Japan, Ltd.ëë
With D. Eldredge and G. Eldredge. 1989. The Fossil Factory. Addison Wesley Publishing Co., Reading, Massachusetts
1991. The Miner's Canary: Extinctions Past and Present. Prentice Hall Books, New York; English edition: Virgin Publishing, Ltd.; Korean edition: Moeum Publishers; Italian edition: Sperling & Kupfer. German Edition: Spektrum; U.S. paperback edition: Princeton University Press
1991. Fossils: The Evolution and Extinction of Species. Photographs by Murray Alcosser. Abrams, New York; Australian edition: Houghton Mifflin; English edition: Aurum Press; German edition: Belser Verlag
(ed.). 1992. Systematics, Ecology and the Biodiversity Crisis. Columbia University Press, New York
With M. Grene. 1992. Interactions: The Biological Context of Social Systems. Columbia University Press, Cambridge, Massachusetts
1995. Reinventing Darwin: The Great Debate at the High Table of Evolutionary Theory. John Wiley and Sons, New York; English edition: Orion; Italian edition: Giulio Einaudi Editore
1995. Dominion. Henry Holt and Co; paperback edition, University of California Press, 1997
1998. Life in the Balance: Humanity and the Biodiversity Crisis. Princeton University Press. Portugal: Dinalivre; China/Taiwan: International Publishing Co.; Poland: Proscynski; Japan: Seidosha; Spain: TusQuets; Italy: Giulio Einaudi Editore
1999. The Pattern of Evolution. W. H. Freeman and Co., New York
2000. The Triumph of Evolution...And the Failure of Creationism. W.H. Freeman and Co., New York
(ed.). 2002. Life on Earth: An Encyclopaedia of Biodiversity, Ecology and Evolution. ABC-CLIO, Santa Barbara, California
2004. Why We Do It: Rethinking Sex and the Selfish Gene. W.W. Norton, New York
2005. Darwin: Discovering the Tree of Life. W.W. Norton, New York
2014. Extinction and evolution : what fossils reveal about the history of life, ISBN978-1-77085-359-1; Firefly Books, Toronto
2014. Concrete Jungle. New York City and Our Last Best Hope for a Sustainable Future. University of California Press, Oakland.
2015. Eternal Ephemera: Adaptation and the Origin of Species from the Nineteenth Century through Punctuated Equilibria and Beyond. Columbia University Press, New York, New York.
2016. With T. Pievani, E. Serrelli, and I. Tëmkin (eds.). Evolutionary Theory. A Hierarchical Perspective. University of Chicago Press, Chicago.
Eldredge possesses a chart of the historical development of cornets (the musical instruments), which he uses as a comparison with that of the development of trilobites. The differences between them are meant to highlight the failures of intelligent design by comparing a system that is definitely designed, with a system that is not designed.