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.

The journeys of the Voyager probes is put in the context of the Netherlands in the seventeenth century, with a centuries-long tradition of sailing ship explorers, and its contemporary thinkers (such as Constantijn Huygens and his son Christian). Their discoveries are compared to the Voyager probes' discoveries among the Jovian and Saturn systems. In Cosmos Update, image processing reconstructs Voyager’s worlds and Voyager’s last portrait of the Solar System as it leaves is shown.

Ideas about time and space are explored in the changes that constellations undergo over time, the redshift and blue shift measured in interstellar objects, time dilation in Albert Einstein's theory of relativity, the designs of both Leonardo da Vinci and spacecraft that could travel near light speed, time travel and its hypothetical effects on human history, the origins of the Solar System, the history of life, and the immensity of space. In Cosmos Update, the idea of faster-than-light travel by wormholes (researched by Kip Thorne and shown in Sagan’s novel Contact) is discussed.

James Cameron journeys to some of the Earth's deepest, most extreme and unknown environments in search of the strange and alien creatures that live there. Joining him is a team of young NASA scientists and marine biologists who consider how these life forms represent life we may one day find in outer space not only on distant planets orbiting distant stars, but also within our own solar system.
Aliens of the Deep is the result of expeditions to several hydrothermal vent sites in the Atlantic and the Pacific. These are violent volcanic regions where new planet is literally being born and where the interaction between ocean and molten rock creates plumes of super-heated, chemically-charged water that serve as oases for animals unlike anything ever discovered. Six-foot tall worms with blood-red plumes and no stomach, blind white crabs, and a biomass of shrimp capable of 'seeing' heat all compete to find just the right location in the flow of the super-heated, life-giving water or to fry.