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).

The story begins with Tyson sitting at a campfire, and telling how the wolf changed through artificial selection, and selective breeding into the dog breeds around today. He then enters the Ship of Imagination, and explains natural selection with the process that helped to create the polar bears. Along the way he talks about DNA, genes and mutation. Next he goes to a forest and describes the Tree of life, this leads him to discussing the evolution of the eye. He then discusses extinction, by going to a monument called the Halls of Extinction, dedicated to the broken branches of the tree of life. Explaining the five great Extinction events. He then tells how some life has survived, and then focuses on the tardigrade. From there he talks about what other kinds of life might have been created on other worlds. He then goes to Saturn's moon Titan. From there he speculates about life and how it first began. He then returns to Earth and tells about abiogenesis and how life changed and evolved. The show ends with an animated sequence from the original series of life's evolution from one cell to humans.