Born in New York City, Sagan studied at the University of Chicago where he obtained his BS in 1955 and his PhD in 1960. He was a research fellow at the University of California, Berkeley, from 1960 to 1962 when he moved to the Smithsonian Astrophysical Observatory in Cambridge, Massachusetts, working at Harvard as lecturer then assistant professor. In 1968 he moved to Cornell where he was appointed director of the Laboratory for Planetary Studies and in 1970 became professor of astronomy and space science. Sagan's main work has been on virtually all aspects of the solar system. One major line of research has been on the physics and chemistry of planetary atmospheres and surfaces, especially of Mars. His other primary interest is the origin of life on Earth and the possibility of extraterrestrial life and he has done much to interest the general public in the new field of exobiology. In laboratory experiments simulating the primitive atmosphere of Earth, he and his colleagues have shown how a variety of organic molecules, such as amino acids, which are the building blocks of proteins, can readily be produced. The energy sources used in these syntheses have included ultraviolet radiation, which would have flooded the Earth's primitive atmosphere, and high-pressure shock waves. It was while working with C. Ponnamperuna and Ruth Mariner at NASA's exobiology division in 1963 that he showed how the fundamental molecule adenosine triphosphate, ATP, could have been produced. ATP is the universal energy intermediary of living organisms and without its presence it is difficult to see how life could have ever originated on Earth.

In 1984 Sagan coauthored, with R. Turco, O. Toon, T. Ackerman and J. Pollock, an influential paper, Nuclear Winter: Global Consequences of Multiple Nuclear Explosions, referred to since as the TTAPS paper. The authors argued that even a relatively small-scale nuclear bomb of 5000 megatons would create enough atmospheric smoke (300 million tons) and dust (15 million tons) to produce a temperature drop of 20–40°C, which would persist for many months. This prolonged nuclear winter would destroy much of the world's agriculture and industry. The impact of the paper on politicians and the public was dramatic.

The nuclear-winter argument itself was heavily criticized by scientists. “These guys don't know what they are talking about,” commented Richard Feynman, and Freeman Dyson dismissed the paper as an “absolutely atrocious piece of science.” The meteorologist S. Schneider pointed out that the TTAPS model was one-dimensional in that it represented only the vertical structure of the atmosphere and ignored the oceans and seasonal changes. It was, he concluded, “a first generation assessment whose conclusions would have to be modified,” and claimed that it threatened more a ‘nuclear fall’ than a nuclear winter.

Sagan has written extensively on the results of planetary science. His Cosmic Connection (1973) introduced these results to a wider audience. His later works The Dragons of Eden (1977) and Broca's Brain (1979) have tried to do the same for recent advances in the theory of evolution and neurophysiology. In a further work, Cosmos (1980), based on a major TV series, Sagan charted the history of physics and astronomy. His later books include Pale Blue Dot: A Vision of the Human Future in Space (1994) and The Demon-Haunted World (1996).