3001 follows the adventures of Frank Poole, an astronaut who was deliberately killed by HAL 9000 in 2001: A Space Odyssey by casting him out into space. His body is discovered in the Kuiper belt, beyond the orbit of Neptune, by the comet-collecting space tug Goliath, after drifting in space for a millennium, and brought back to life, deep-freezing to near absolute zero having preserved him sufficiently for the advanced medical technology of the time to be able to revive him. He then explores the Earth of 3001, notable features of which are the BrainCap, a technology which interfaces computers directly with the human brain, genetically engineered dinosaur servants, and four huge space elevators spaced around the Earth's Equator connected by a spaceport ring in geostationary orbit. Humanity has also colonized Jupiter's moons Ganymede and Callisto.

In the 26th century, the monolith in Olduvai Gorge, Africa (dubbed TMA-0) that kickstarted human intellectual evolution, has been discovered. TMA-1, the monolith found on the moon, had earlier been brought to Earth in 2006 and erected in front of the United Nations Building in New York City.