In prehistoric Africa, Moon-Watcher, a man-ape with the first inklings of human intelligence, encounters a strange monolith. The monolith influences Moon-Watcher and the rest of his tribe, rewiring their brains to feel dissatisfaction and desire and teaching them survival skills. Thus equipped, Moon-Watcher, the most enterprising and promising of the man-ape pupils, fashions a weapon from a stone, killing a hog to feed his tribe. Later, Moon-Watcher kills a predatory jaguar, as well as the competing tribe’s leader, One-Ear. Together, these feats signal a new era for the man-apes: with their new skills, the previously docile simians are now capable of exerting dominance not only on the Earth, but on one another.
Over millions of years, these man-apes evolve, the course of their evolution profoundly shaped by the monolith’s teachings. Their newfound affinity for tools not only makes them smarter —resulting in even better tools—but also reshapes their bodies, eliminating the need for claws and large teeth and encouraging the development of more dexterous hands. Gradually, the man-apes become recognizably human. They develop language and writing and culture, but also increasingly deadly weapons. By the present day, humans are the undisputed masters of the world, but live under the ever-present threat of nuclear war.
In 1999, Dr. Heywood Floyd travels to Clavius Base on the moon aboard the enormous Orion III spacecraft. On his journey, he contemplates humanity’s technological advancements, and evades questions about the circulating story about a moon pandemic. Landing at the base, Floyd thanks the scientists for going along with the epidemic cover-story, then receives a briefing on TMA-1, a mysterious black slab excavated from Tycho crater. Its discovery sparks debates about intelligent alien life, with scientists dating its origin to over 3 million years ago. Floyd and others arrive to visit the monolith just as sunlight hits it for the first time. It emits a shrieking sound and a radio signal traced to Iapetus, a moon of Saturn.
A few months later, David Bowman, the captain of Discovery One, is 30 days out from Earth. Though originally bound for Jupiter, he and his crewmate, Frank Poole, have recently been informed the spacecraft will continue on to Saturn. Once there, the other three crewmates will wake from their hibernation pods. Though Hal, the ship’s onboard artificial intelligence computer, oversees Discovery One’s operating functions, Bowman and Poole still keep busy, each following a meticulous 24-hour schedule. Despite their isolation from the rest of humanity, this schedule keeps both human crewmates sane, and their trip to Jupiter is a frictionless one.
Entering Jupiter's orbit, Bowman and Poole marvel at the size of the planet. After taking photos and measurements, they send two probes into its atmosphere. Only one survives, but it reveals, via live video feed, a mesmerizing ocean of golden gas beneath the outermost clouds. The first phase of the mission completed, Discovery One departs for Saturn, picking up speed on its way out. Within days of leaving, however, Hal reports an imminent malfunction with the ship’s radio communication device, the AE-35 unit. Without it, the ship cannot communicate with Earth.
Using “Betty,” a space pod designed for extra-vehicular repairs, Poole replaces the AE-35 unit on the outside of the ship. Upon inspection, however, nothing seems to be wrong with the unit. Unsure what to do—Hal is supposed to never make an error—they report the problem to Mission Control. Mission Control confirms their results and suggests they may need to temporarily disconnect Hal; however, they have to conduct more testing to be sure. In the interim, Hal reports the imminent failure of the second AE-35 unit.
Mission Control reports back, confirming its initial diagnosis and instructing them to disconnect Hal. Before finishing, however, the video feed cuts off, and Hal reports the unit has failed. Poole takes “Betty” out to retrieve the faulty unit for study, but as he does the space pod—under Hal’s control—crushes him against the ship. Uncertain of Hal’s role in Poole’s death, Bowman decides to wake the other crewmates for support. However, Hal refuses to grant him manual override for the hibernation units, relenting only after Bowman threatens him with disconnection.
Bowman wakes the other crew members, but as he does so the ship’s airlocks open, sucking the ship’s atmosphere into space. Bowman secures himself in an emergency shelter, but the other crew members suffocate. To protect himself, Bowman shuts down Hal’s higher functioning in the ship’s computer main frame, witnessing the regression of Hal’s identity. Re-establishing contact with Earth, Bowman learns of the mission's true purpose to travel to Iapetus in search of alien life, and of Hal’s motivations for turning on his crewmates. Forced to lie about the mission’s true objectives, Hal experienced a program conflict, resulting in his errors. Then, threatened with temporary disconnection, Hal acted to defend himself, believing disconnection to mean death.
Bowman continues the mission to Iapetus alone, traveling for several months. He keeps busy repairing the ship and contemplating the mysteries lying ahead. Conscious of being the sole representative of humanity, he works to maintain his appearance and sanity. As the ship approaches Iapetus, Bowman notes a small black dot at the center of the moon’s white surface. Upon closer inspection, Bowman realizes it is a second monolith, many times larger than the first; though it lacks the same magnetic anomaly as the first, Mission Control names it “TMA-2.” Bowman completes the final maneuver of Discovery One, successfully maneuvering it into orbit around Iapetus.
Bowman takes a space pod to the roof of the second monolith. As he nears, the monolith activates, opening and pulling him down into it. Bowman’s last words to Mission Control describe the monolith as being “hollow” and “full of stars.” The monolith transports Bowman across the universe, treating him to a variety of extraordinary sights, including an interstellar transit system, a ruinous ancient shipyard, and a double-sun inhabited by plasma-based life-forms. Finally, Bowman is taken to an Earth-style hotel suite, designed to put him at ease. However, close inspection reveals the suite to be alien-made and artificial. Bowman goes to sleep in a bed.
The weaver, one of the monolith’s original creators, reshapes Bowman’s mind. His race transcended their bodily form long ago and have since committed themselves to cultivating intelligent life across the universe. As the alien tampers with his mind, Bowman’s life flashes before his eyes and many of the mysteries of the universe are revealed. Reborn as the Star Child, he returns to Earth, looking upon it as a “glittering toy” and destroying the planet’s orbiting arsenal of nuclear warheads. The new master of the world, he contemplates his plans for Earth.