Carl Sagan opens the program with a description of the cosmos and the Spaceship of the Imagination. The ship journeys through the universe's hundred billion galaxies, the Local Group, the Andromeda Galaxy, the Milky Way, the Orion Nebula, our Solar System, and finally the planet Earth. Eratosthenes' successful calculation of the circumference of Earth leads to a description of the ancient Library of Alexandria. Finally, the Ages of Science are described, before pulling back to the full span of the Cosmic Calendar.

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).

Beginning with the separation of the fuzzy thinking and pious fraud of astrology from the careful observations of astronomy, Sagan follows the development of astronomical observation. Beginning with constellations and ceremonial calendars (such as those of the Anasazi), the story moves to the debate between Earth and Sun-centered models: Ptolemy and the geocentric worldview, Copernicus' theory, the data-gathering of Tycho Brahe, and the achievements of Johannes Kepler (Kepler's laws of planetary motion and the first science-fiction novel).

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.

The episode, devoted to the planet Mars, begins with scientific and fictional speculation about the Red Planet during the late nineteenth and early twentieth centuries (H. G. Wells' The War of the Worlds, Edgar Rice Burroughs' science fiction books, and Percival Lowell's false vision of canals on Mars). It then moves to Robert Goddard's early experiments in rocket-building, inspired by reading science fiction, and the work by Mars probes, including the Viking, searching for life on Mars. The episode ends with the possibility of the terraforming and colonization of Mars and a Cosmos Update on the relevance of Mars' environment to Earth's and the possibility of a manned mission to Mars.