Wood travels through war-torn Afghanistan, crossing the Oxus River into Central Asia and the Silk Road city of Samarkand where, in a drunken brawl, Alexander killed the friend who had previously saved his life.

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

In the fifth episode of the series, Morgan Freeman sets to examine the nature of evil, visiting a serial killer in prison and witnessing an exorcism in India. He also explores ancient beliefs, including Zoroastrianism.