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.

Beginning with the origins of the universe in the Big Bang, Sagan describes the formation of different types of galaxies and anomalies such as galactic collisions and quasars. The episodes moves further into ideas about the structure of the Universe, such as different dimensions (in the imaginary Flatland and four-dimensional hypercubes), an infinite vs. a finite universe, and the idea of an oscillating Universe (similar to that in Hindu cosmology). The search into other ideas such as dark matter and the multiverse is shown, using tools such as the Very Large Array in New Mexico. Cosmos Update shows new information about the odd, irregular surfaces of galaxies and the Milky Way perhaps being a barred spiral galaxy

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.