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On the planet Karn, an insect-like alien crawls away from an escape pod. It is ambushed and killed by Condo, a large man with a hook for a hand, who takes its head to a castle and his master Solon. However, the head is unsuitable — Solon needs a humanoid, warm-blooded and with a central nervous system.
The TARDIS materialises on Karn in the middle of a lightning storm, and the Fourth Doctor rushes out, ranting at the Time Lords for diverting him to this planet. Sarah suggests that perhaps the TARDIS malfunctioned again, but the Doctor is insistent there is something going on which the Time Lords do not want to sully their hands with. While the Doctor sulks, Sarah finds the escape pod, and climbing to a higher point, sees a valley filled with wrecked spacecraft.
She comes across the headless body of the alien and gasps, which finally attracts the Doctor's attention. The Doctor identifies it as a Mutt. He also now recognises the stars — his homeworld is within a couple of billion miles from this planet. Sarah spots the castle just as it starts to rain, and the two travellers make for it, all the while observed by a girl in a strange headdress.
The girl, Ohica, reports to the elderly Maren, the leader of the Sisterhood of Karn. Maren does not believe Ohica at first, insisting that no ship could approach Karn without attracting their honed senses. Maren shows Ohica the Flame of Life, which is burning low. Without the Flame, there is no Elixir, and there has not been for over a year — the chalice stands empty. The secret of the Elixir is known only to the Sisterhood and the High Council of the Time Lords, with whom they shared the Elixir. Now, there is none left, except for the few vials they have kept for themselves. Maren fears that the Time Lords have sent agents to steal the Elixir. Maren tells Ohica to summon the other sisters to form a circle.
In the castle, Solon scolds Condo, warning him that if he does not obey him, he will not reattach Condo's arm. The Doctor and Sarah ring the doorbell, seeking shelter. Solon is delighted at the arrival of humans, and welcomes the two, complimenting the Doctor on his "magnificent" head. The Doctor notices a clay bust, but Solon quickly draws a sheet over it. When the Doctor asks Solon about the Mutt and the wrecked ships, Solon suggests that it is due to the magnetic radiation around the planet. Solon rescued Condo from one such starship, and had to amputate his arm to save his life.
The Sisterhood chant "Sacred Fire, Sacred Flame" in a circle, allowing Maren to see the TARDIS reflected in her ring. Concentrating further, they make the TARDIS materialise in their shrine in the midst of a strange mist. Examining the ship, Maren identifies it as a Time Lord vessel, and concludes that the Doctor is here on their behalf to steal the elixir. The Sisterhood's powers can overwhelm most others and drive them insane, but the Time Lords are their equals in mind power. The circle continues to chant, seeking the Doctor.
The Doctor knows of Solon, who was an authority on microsurgical techniques and tissue transplants. He remarks that Solon's disappearance caused quite a stir and there were rumours that he had joined the Cult of Morbius. The Doctor now recognises the clay head — it is that of Morbius, one of the most despicably criminal minded Time Lords in history. Before he can say anything further, the drugged wine takes its effect, and the Doctor falls over unconscious as does Sarah.
Solon and Condo take the Doctor's body to the laboratory, not realising that Sarah was only feigning unconsciousness. In the laboratory, Solon's examination of the Doctor confirms he is a Time Lord. Condo is concerned about their power, but Solon dismisses them as spineless parasites. Morbius offered them power, but they rejected it, and they will now feel the power of his revenge. Needing proper lighting for the operation, Solon and Condo go to repair the generators that have been knocked out by the storm. Once they leave the room, however, the Doctor's body vanishes in the same mist the TARDIS did.
Sarah keeps hidden as Solon and Condo pass, and enters the lab. She draws back the curtain on a bed, thinking it is the Doctor, but as the lights come up, she sees a headless, patchwork creature made from various body parts. It sits up...
Sarah moves away from it quickly, but hears Solon and Condo returning to the laboratory and has to hide. Solon finds the Doctor gone, and concludes that it must be the work of the Sisterhood. Solon swears revenge, and he and Condo go to get the Doctor's body back.
The Doctor regains consciousness to find himself surrounded by members of the Sisterhood. Maren accuses him of being sent by the Time Lords to steal the Elixir. The Doctor denies this, saying that the last thing he remembers is having wine with Solon and Morbius... but Morbius is dead, executed by the Time Lords on Karn for leading a rebellion. His body was placed in a dispersal chamber and atomised. The Doctor realises that just before he passed out, he felt the mind of Morbius. Maren refuses to believe that Morbius is alive and says that the Doctor will join him in death shortly.
Sarah trails Solon and Condo as they make their way towards the shrine. They observe the Sisters gathering wood to burn the Doctor at the stake. The Doctor points out that the Time Lords have always been friendly to the Sisterhood — they saved them when Morbius overran the planet. Maren retorts that this was out of self-interest as they needed the Elixir. Ohica reveals that the Flame is dying. The Doctor is puzzled, as the Flame is fed by gases from deep within the planet and should last for millions of years unless there has been some subterranean movement. They tie the Doctor to the stake while chanting the Song of Death. The Doctor warns them that if the gases are sealed in, the mountain could explode.
Solon and Condo interrupt the ceremony, to Maren's anger. Solon asks them to spare the Doctor, even offering Condo in his place. When that is denied, he begs them to give him the Doctor's head. While Maren dismisses Condo and Solon, a disguised Sarah sneaks up behind the Doctor and cuts his bonds. The ceremony starts again, and as the flames lick up, Maren's eyes close. The Doctor and Sarah take the opportunity to slip away, but Maren spots them, hitting Sarah with a blue bolt from her ring before they get away.
Back at the castle, Condo is angered by Solon's offer to sacrifice him, and threatens to kill Solon. Pleading for his life, Solon offers to restore Condo's arm and tells him to prepare the laboratory. Meanwhile, Sarah and the Doctor have escaped the shrine, but Sarah has been blinded by the energy from Maren's ring. She is worried that it may be permanent, but the Doctor assures her that the flash merely numbed the optic nerves and she should recover in a few hours. Despite Sarah telling him about the headless body she saw, the Doctor leads them back towards Solon's castle.
Solon speaks with a tremulous voice he addresses as Morbius. Solon asks for more time, but Morbius is impatient. Condo calls from above: the Doctor and Sarah have arrived. The Doctor asks him to examine Sarah's eyes, and they go to the laboratory. As Solon does so, the Doctor finds the headless body hidden behind the curtain. Condo escorts Sarah back to the parlour, while the Doctor speaks to Solon. Solon tells him that Sarah's retinae have been almost completely destroyed, but there is one chance: the Elixir of Life. Despite the risks, the Doctor must return to the shrine.
Solon summons Condo, who leaves Sarah in the parlour. Solon gives a note for Condo to pass to the Sisterhood before the Doctor gets there. Sarah hears Morbius's voice calling for Solon. Following the sound, she enters a hidden laboratory. As she stumbles blindly towards Morbius, who is a glowing brain in a tank, he accuses her of being a part of the Sisterhood, sent here to destroy him...
Solon enters and drags Sarah out of the laboratory. As he closes the door, Sarah hears Solon address the voice as "Morbius" and hears how Solon has sent the Doctor into a trap. Sarah locks Solon in the laboratory and, still blind, makes her way out of the castle.
In the shrine, Maren gives five of the Sisters, including Ohica, the last of Elixir. Only these five will survive when the Flame finally dies. The letter from Solon arrives, and Maren tells Ohica to warn the guards. When the Doctor enters the tunnels, a net falls on him and he is surrounded. When he explains why he came back, Maren tells him that the effects of the ray are not permanent, and Solon knows that. Maren demands to know why the Doctor is here, if it is not to steal the Elixir, and the Doctor replies that he feels something evil is brewing, something to do with Morbius.
Maren still does not believe — she saw Morbius being dispersed. The Doctor asks if Solon was here at that time, and Maren says many came to Karn at the time. Morbius led an army of mercenaries, promising them the Elixir and immortality and revealing its existence to the cosmos. The Doctor tells Maren that if she wants his help, the wrecking of spaceships simply passing by Karn has to stop. Outside, Sarah continues to work her way along the rocks and runs into Condo, who had orders to find her. He tells her the Doctor is dead and carries her, struggling, back to the castle.
The Doctor persuades Maren to let him see the Flame, the first one outside the Sisterhood to see it. The Doctor admires the process — the heat of the Flame causes oxidation of chemicals in the surrounding rocks, with the reaction of superheated gases forming drops of the Elixir. The Doctor insists the process is not mystical and with analysis, the Elixir could probably be synthesised, but the consequences would be disastrous with everyone trying to live forever. Even the Time Lords only take it in rare cases, not regularly like the Sisterhood, who because of it have become stagnant, unchanging, without progress.
The Doctor takes something from his hair that turns out to be a firework and puts it in the Flame, seemingly extinguishing it. Horrified, Maren orders the Doctor killed, but the flames ignite again, brighter than ever. It was merely soot that was blocking the gases.
At the castle, Sarah is bound hand and foot and lying on a table. Solon rants about how others called him insane, and only Morbius believed in him. When Solon tells Morbius that the Doctor is a Time Lord, Morbius calls him a fool — that means that the Time Lords have tracked him down and will return in force. Morbius insists that he be transferred into the body now, and asks about the artificial brain casing Solon once constructed. Solon protests that he abandoned it because there was no way to stop the static electricity build-up, which risked severe pain and seizures. Morbius tells him that he will take his chances.
Back in the castle, Solon prepares to operate, but Condo is enraged when he recognises his lost arm attached to the patchwork body. He attacks Solon, who shoots him in the belly. As the two struggle, Morbius's brain falls to the floor. Not knowing what damage has been done, Solon places the fallen brain in the casing, releasing Sarah so she can assist in the operation. If Morbius dies, so does she.
The wounded Condo crawls into the hallway as outside, the Sisters carry the Doctor's seemingly dead body through the lightning storm. In the meantime, the operation is finished — within minutes Morbius will live again. Solon goes to answer the door bell, and sees the Sisters leaving the Doctor's body in the parlour. In the laboratory, Sarah's eyesight starts to clear, but the monstrous body of Morbius gets off the operating table and lumbers towards her...
Sarah screams as she sees the Morbius creature, and dodges out of the way. She warns Solon that the creature is loose and he runs back to the laboratory. Sarah notices the Doctor's body, but as she approaches, the Doctor wakes up and smiles at her. He is here to stop Solon, but Sarah tells him it is too late.
Morbius sees his new body in the mirror, and smashes it angrily. Solon tries to calm him down, but Morbius renders him unconscious. When the Doctor meets the creature, he too is struck down. Morbius chases Sarah, but Condo intervenes, knocking Sarah down the stairs into the cellar while he grapples with Morbius. However, Morbius is too strong, and kills Condo instead. Morbius wanders out of the castle as the Doctor regains consciousness. He carries Sarah into the secret laboratory to let her recover.
Solon, too, has awakened, and assembles a tranquiliser gun. He tells the Doctor that the operation was not complete, only the motor functions are working, the rest on an instinctual level. Knowing Morbius's hatred, he will seek out the Sisterhood. Sure enough, Morbius finds one of the sisters in some ruins nearby and kills her. The Doctor and Solon find the body and they search the ruins. Morbius attacks the Doctor, but is knocked out by Solon's tranquiliser. As they carry the creature back to the castle, the Doctor tells Solon that Morbius's brain will be detached and returned to the Time Lords.
The body of the dead Sister is brought back to Maren. Ohica reports that witnesses saw a creature and then the Doctor and Solon hunting for it. Maren realises that Solon has succeeded in his experiments and resurrected their ancient enemy. But Maren is too old and weak to leave the shrine, and she gives Ohica permission to lead the Sisters to the castle.
The Doctor gives Solon five minutes to disconnect the brain as he goes and checks on Sarah. However, Solon locks them in the secret laboratory instead and begins to repair Morbius. Using materials from the secret laboratory, the Doctor makes cyanide gas, which he then pipes through a vent that leads to the operating room above.
Solon has finished the operation, but the gas chokes him and he dies. The alien lungs of Morbius, however, are more robust and the creature walks out of the room unharmed. He goes to confront Sarah and the Doctor — he claims that when the knowledge of his resurrection spreads, his followers will rise in their millions. The Doctor and Sarah mock Morbius in an attempt to overheat his brain, and the Doctor challenges him to a mindbending contest.
They grab hold of the appropriate apparatus in the laboratory and begin. The machine's display begins to show Morbius's brain casing head, then his previous face, then the Doctor, then the Doctor's previous incarnation. Further and further back into the Doctor's past the images go, as Morbius asks, "How far, Doctor? How long have you lived?" The face of the First Doctor fades into a series of eight other faces, all likely Morbius's previous incarnations, then Morbius's brain case shorts out. The Doctor collapses, as Morbius stumbles out in a daze.
Ohica's band of sisters finally reach the castle, and threaten Morbius with lit torches. Ohica goes down to the secret laboratory while the other Sisters herd Morbius out into the mountains. Ohica finds Sarah cradling the dying Doctor. Outside, the Sisterhood chases Morbius over a cliff, where he falls to his death.
Taking the Doctor back to the shrine, Maren says only the Elixir of Life can save him, but there is none left. However, the revived Flame has gathered enough Elixir. There is enough for the Doctor, but not for Maren, who accepts that the Doctor was right: there should be an end. The Elixir is given to the Doctor, who revives almost immediately. Maren steps into the Flame of Life, becoming younger, and then vanishes.
Ohica starts to thank the Doctor, but he stops her, saying that Sarah and he have another engagement. Before they leave, he gives her a pair of curious objects in case they need to relight the Flame again. He says that the magic runes written upon the two cardboard tubes should read 'Thunderflash and Mighty Atom; light blue touch paper and retire immediately.' This time, the TARDIS vanishes in a puff of light and smoke...