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.

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.

The simple act of making an apple pie is extrapolated into the atoms and subatomic particles (electrons, protons, and neutrons) necessary. Many of the ingredients necessary are formed of chemical elements formed in the life and deaths of stars (such as our own Sun), resulting in massive red giants and supernovae or collapsing into white dwarfs, neutron stars, pulsars, and even black holes. These produce all sorts of phenomena, such as radioactivity, cosmic rays, and even the curving of spacetime by gravity. Cosmos Update mentions the supernova SN 1987A and neutrino astronomy.

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

The idea of intelligence is explored in the concepts of computers (using bits as their basic units of information), whales (in their songs and their disruptions by human activities), DNA, the human brain (the evolution of the brain stem, frontal lobes, neurons, cerebral hemispheres, and corpus callosum under the Triune Brain Model), and man-made structures for collective intelligence (cities, libraries, books, computers, and satellites). The episode ends with speculation on alien intelligence and the information conveyed on the Voyager Golden Record.

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.