Sagan discusses the story of the Heike crab and artificial selection of crabs resembling samurai warriors, as an opening into a larger discussion of evolution through natural selection (and the pitfalls of intelligent design). Among the topics are the development of life on the Cosmic Calendar and the Cambrian explosion; the function of DNA in growth; genetic replication, repairs, and mutation; the common biochemistry of terrestrial organisms; the creation of the molecules of life in the Miller-Urey experiment; and speculation on alien life (such as life in Jupiter's clouds). In the Cosmos Update ten years later, Sagan remarks on RNA also controlling chemical reactions and reproducing itself and the different roles of comets (potentially carrying organic molecules or causing the Cretaceous–Paleogene extinction event).

Sagan discusses comets and asteroids as planetary impactors, giving recent examples of the Tunguska event and a lunar impact described by Canterbury monks in 1178. It moves to a description of the environment of Venus, from the previous fantastic theories of people such as Immanuel Velikovsky to the information gained by the Venera landers and its implications for Earth's greenhouse effect. The Cosmos Update highlights the connection to global warming.

Carl Sagan teaches students in a classroom in his childhood home in Brooklyn, New York, which leads into a history of the different mythologies about stars and the gradual revelation of their true nature. In ancient Greece, some philosophers (Aristarchus of Samos, Thales of Miletus, Anaximander, Theodorus of Samos, Empedocles, Democritus) freely pursue scientific knowledge, while others (Plato, Aristotle, and the Pythagoreans) advocate slavery and epistemic secrecy.

Questions are raised about the search for intelligent life beyond the Earth, with UFOs and other close encounters refuted in favor of communications through SETI and radio telescope such as the Arecibo Observatory. The probability of technically advanced civilizations existing elsewhere in the Milky Way is interpreted using the Drake equation and a future hypothetical Encyclopedia Galactica is discussed as a repository of information about other worlds in the galaxy. The Cosmos Update notes that there have been fewer sightings of UFOs and more stories of abductions, while mentioning the META scanning the skies for signals.

Operation Condor was a campaign of political repression and terror involving intelligence operations and assassination of opponents, officially implemented in 1975 by the right-wing dictatorships of the Southern Cone of South America. The program was intended to eradicate communist or Soviet influence and ideas, and to suppress active or potential opposition movements against the participating governments.

Dinosaurs ruled the earth for 150 million years, then suddenly they were gone. Their disappearance is one of the planet’s greatest mysteries – unimaginable, until now. The film proposes a minute-by-minute chronology of the Chicxulub impact and its effect on the dinosaurs and other animals around the world. A blow-by-blow account of the cataclysm that ended the reign of the dinosaurs, and forever changed the course of life on Earth.