The TARDIS travellers land on a moving spaceship and find the crew apparently dead. However, one of the crew members, Captain Maitland, regains consciousness and Ian Chesterton fully revives him and another woman, Carol Richmond. These two tell the travellers that they are on an exploration mission from Earth and are orbiting Sense-Sphere. However, its inhabitants, the Sensorites, refuse to let them leave the orbit. The Sensorites visit and stop the travellers from leaving, while sending them on a collision course, which the Doctor diverts. The travellers then meet John (whose mind has been broken by the Sensorites) and find out that he is Carol's fiancé.
Returning to plague the crew, the Sensorites freeze Carol and Maitland once more. The Doctor breaks Maitland's mental conditioning, but cannot help John. Susan's telepathic mind is flooded with the many voices of the Sensorites who remain scared of the humans and are trying to communicate with her. Meanwhile, The Doctor works out that the Sensorites attacked the human craft because John, a mineralogist, had discovered a vast supply of molybdenum on Sense-Sphere. Susan reports that the Sensorites want to make contact with travellers, asking the crew to go aboard Sense-sphere and reveal that a previous Earth expedition caused them great misery. The Doctor refuses but Susan, under duress, agrees and departs.
The Doctor deduces that the Sensorites need plenty of light, so Ian reduces the lighting on the ship, in a bid to rescue Susan. As a result, Susan returns to the spacecraft. The Doctor then asks the Sensorites to return his lock and is invited to go to Sense-Sphere to speak with the leader. Susan, Ian, Carol and John join him while Barbara and Maitland stay behind. John is promised that his condition will be reversed. On their journey to Sense-Sphere, the party learn that the previous visitors from Earth exploited Sense-Sphere for its wealth, then argued. Half of them stole the spacecraft, which exploded on take-off.
The Sensorite Council is divided over the issue of inviting the party to Sense-Sphere: some of the councillors plot to kill them on arrival, but some believe that the humans can help with the disease that is currently killing many Sensorites. Their first plot is foiled by the other Sensorites, but they continue to plot in secret. The humans are not told of the first plot, and John and Carol are cured. In the main conference room, Ian starts coughing violently and collapses. Suffering from the disease that has blighted the Sensorites, he is told that he will soon die.
It turns out that he was actually poisoned by drinking water from the general aqueduct. The Doctor finds the problematic aqueduct and starts work with the Sensorite scientists. The plotting Sensorites capture and then impersonate a Sensorite leader, the Second Elder and steal the new cure, before it is given to Ian, but a new one is made easily and Ian is cured.
Meanwhile, investigating the aqueduct, the Doctor finds strange noises and darkness. He finds and removes deadly nightshade (the cause of the poisoning), but on going back, meets an unseen monster. Susan and Ian find him unconscious with a ripped coat, but otherwise unharmed. On being recovered, he tells of his suspicion that some Sensorites are plotting to kill them. The plotting Sensorites kill the Second Elder and one of them replaces him in his position.
John tells the others that he knows the lead plotter, but he is now too powerful, so The Doctor and Carol go down to the aqueduct to find the poisoners. Their weapons and map were tampered with and are useless.
Elsewhere, a mysterious assailant abducts Carol and forces her to write saying she has left for the ship. Neither Susan, John or Barbara believe this so they go to investigate and find her imprisoned. Susan, John and Barbara overpower the guard and release Carol. On finding out about the tampered tools, they go into the aqueduct to rescue the Doctor and Ian. The leader discovers the plotters a little while later.
Ian and the Doctor discover that the monsters were actually the survivors of the previous Earth mission, and they had been poisoning the Sensorites. Their deranged Commander leads them to the surface, where they are arrested by the Sensorites. The Doctor and his party return to the city, pleading clemency for the poisoners. The leader of the Sensorites agrees and sends them back with Maitland, John and Carol to Earth, for treatment for madness.