In Avery's cabin, the Doctor tries to explain that the TARDIS sensors picked up a distress call. However, they are held at gunpoint by Avery and told that there is only one barrel of water to sustain all of them until the wind picks up so the Doctor and Rory must walk the plank. Amy is sent to the galley where she finds a trunk full of swords. As the Doctor is about to jump off the plank Amy appears, brandishing a sword. She terrifies the crew who try to fend her off with sticks and rope. One of the crew is accidentally cut as he struggles with her. He declares himself a dead man. No sooner has he been cut than a black spot appears on his hand. A second fight leads to Amy dropping the sword, cutting Rory. A Black spot appears on his palm.
The woman's voice is heard singing again. Rory and the pirate are both overcome and act as if drunk. A beautiful woman, lit by an eerie green light, flies up from the waves onto the deck. She reaches her hand out to the pirate who takes it willingly: he vapourises immediately. The crew and the time travellers run below deck where they find themselves knee deep in water. Avery tells the Doctor that the woman is a demon, the Siren, who lusts after blood. Any injury will attract her.; Avery refers to the woman as a Siren, and she has been taking every injured crew member, whether the wound is large or small.
One of the crew is bitten by a leech. Everyone climbs out of the water a black spot appears on the man's hand. The Doctor says that there is three inches of timber between them and the siren but she appears anyway. After she takes the crewman the Doctor guesses that she is using water as a portal. To keep themselves safe they go to the powder room, the driest place on the ship. They find the door unlocked and inside is Toby, Avery's young son who has stowed away to meet the "honorable Navy captain" his mother told him about before she died. Toby is very ill, and soon a black spot appears on the palm of his hand. The Doctor realises that the Siren is not after blood: she comes for the sick as well as the bleeding. The Doctor tells Avery that their only escape is in the TARDIS. As the two men prepare to leave, the captain gives his son a mermaid medallion.
The Doctor leads Avery into the TARDIS, where the pirate captain soon shows he is at home with the concept of the Doctor's ship and finds it comparable to his own. The two surviving crewmen, the boatswain and Mulligan plan to leave the ship along with Avery's treasure. Toby learns from them that his father is a pirate. In response, the boy cuts the boatswain's hand with a sword, meaning that the man cannot leave the armoury. Mulligan leaves without him. As this happens, the Doctor discovers that the TARDIS cannot recognise its location; the plane on which it is standing is unfamiliar to it. It suddenly grinds into life. Despite the Doctor's efforts, it begins to dematerialize. The Doctor tells Avery that he has no idea where the TARDIS might take them and they abandon ship.
They encounter Mulligan on the deck. He is carrying Avery's treasure. He opens fire on them with two pistols and then locks himself in a cabin and lights a match, accidentally burning his hand; he is taken by the Siren. When the Doctor and Avery go into the room they see that there is no water present and the Doctor revises his theory. He has deduced that the Siren can use any reflective surface as a portal. They remember that Toby has Avery's medallion so they rush to the armoury. The Doctor breathes on the medallion to mist up the surface to stop the siren coming. He and Avery then go to the captain's cabin where the Doctor smashes the mirrors and windows and throws all of the captain's treasure overboard. He tells Avery to find the jewelled crown that Mulligan was stealing and dispose of it.
Avery, Toby, Rory and Amy are sleeping. Amy awakes to see a woman with an eye patch staring at her through a hatch in the side of the ship. The hatch disappears after the woman closes it. Amy goes to Avery's cabin and finds the Doctor. She is about to mention the woman when he tells her he feels as though he is being watched. A sudden storm makes everyone go on deck and, as they struggle with the sails, Avery tells his son to fetch his coat. As the boy does so, the jewelled crown falls out and rolls across the deck. The Siren appears and takes Toby.
Rory is knocked into the sea by a sudden movement of a spar. Amy says that she is going in to rescue him but the Doctor says that the only hope is to release the Siren. He takes a lid from the water barrel and the Siren emerges and plunges into the sea after Rory. The Doctor says that he thinks the Siren is intelligent and can be reasoned with: perhaps the others are still alive. He pricks his own hand and those of Amy and Avery. The black spots appear on their palms and the Siren returns for them.
They wake up in a spaceship. The Doctor explains that it is in the same space as the pirate ship. His feeling that they were all being watched is borne out by the fact that the windows on the spaceship face onto the Fancy. Amy says that the distress signal was coming from the spaceship. They make their way through the craft and discover the bodies of the crew who, the Doctor thinks, died of an Earth virus or bacteria.
They enter the sick bay and see Avery's crew, Rory, Toby, and the TARDIS. The humans are attached to life support machines. Amy tries to detach Rory causing the Siren to appear and sing him to sleep. The Doctor realises that her voice is an anaesthetic and that she is a virtual doctor who has been caring for the injured humans since her own crew died. As she cannot cure them she leaves them in stasis and tends to them. The Siren won't let Amy help Rory until she recognises that he is her husband. Then the Siren holds out her hand, with a glowing ring around her wrist. The Doctor says that this is a consent form and Amy must put her hand through the ring. Once this is done they have to face the fact that Rory is on the point of death. He tells Amy to perform CPR on him, which she does, in order to save his life.
The Doctor tells Avery that Toby has typhoid fever, and if he were to leave the ship he would die in months. Avery says he will stay on the ship to look after his son. He tells the Doctor to point him at the "atom accelerator" and he will fly the ship away so that the Siren does not try to treat all of humanity. The pirates take up their positions in the ship and head out to the stars.
Back in the TARDIS, Amy and Rory say good night to the Doctor. He calls her "Amelia," which Amy says is a sure sign that he is worried about her. The Doctor replies that he is always worried about her. She has a flashback to his death on the beach in Utah and says that it is mutual. The Doctor secretly scans Amy for pregnancy again. The result is still both positive and negative.