In the near future, Earth's energy crisis has led to the harvesting of helium-3 from the moon's surface as a primary source of power. The Lunar Industries mining base is nearly fully automated, except for a lone human operator, who is stationed on the moon to oversee operations and send the helium-3 back to Earth. The current operator is a man named Sam at the end of his three-year contract, looking forward to returning home to his wife and young daughter. He lives a monotonous but functional life, assisted only by an intelligent computer named GERTY, which manages the base's day-to-day activities and takes care of his needs.

As his tenure nears an end, Sam's health begins to deteriorate, and he suffers from headaches and hallucinations. One day, while conducting a routine inspection on a lunar rover, he crashes due to a sudden vision, and the accident leaves him unconscious. However, he wakes up in the base's infirmary with no memory of the accident. GERTY is evasive about the details of Sam's recovery, which prompts Sam to mistrust the situation and seek answers. He begins to feel a pervasive sense of isolation and suspicion, compounded by mysterious occurrences that challenge his understanding of his sole presence on the lunar base.