Silas Heap, the father of Septimus Heap — who is apprenticed to Marcia Overstrand, ExtraOrdinary Wizard — uses his magic to UnSeal a room in the palace so he can keep his game pieces from getting lost. Unfortunately, that allows the Substantial Spirit of Queen Etheldredda the Awful and her pet Aie-Aie —a rat-like creature — to be released. She finds her way to Princess Jenna and introduces herself. Jenna has an immediate dislike of the ghost.
Septimus has developed an interest in the writings of Marcellus Pye, an ancient alchemist. Septimus is especially interested in the area of Physik, learning how to heal people using herbal medicines. Marcia is unhappy as she considers both Alchemy and Physik to be useless areas of study. She demands Septimus return to studying for his next Apprentice exam.
Later, the ghost of Alther Miller, a former ExtraOrdinary Wizard, asks Septimus to take a late night walk to The Hole in the Wall Tavern, a place for ghosts to congregate. The living are only allowed in if two ghosts have asked them. Septimus discovers that Queen Etheldredda has asked to meet him.
She whispers the name of Marcellus Pye to him, telling him to meet the alchemist at midnight at Snake Slipway. As Alther and Septimus make their way back to the palace, they run into Sarah Heap, Septimus’ mother. She has been called to the infirmary to help with a strange Sicknesse that is occurring in the city. Alther and Septimus accompany her to the boatyard to keep her safe in the dark. His brother Nicko and Alther take her the rest of the way to the infirmary.
Septimus decides to disobey Alther and Marcia’s orders to stay away from Marcellus Pye and sneaks off to the Snake Slipway. When he arrives, he sees fire burning beneath the water. When he looks closer, Queen Etheldredda pushes him into the water. Septimus almost drowns as an undertow carries him far from the Slipway. He finds himself pulled into a tunnel that leads to the palace and his adopted sister, Jenna. Queen Etheldredda appears and tells Jenna that she has Reclaimed Septimus by saving his life. The queen makes Jenna promise to bring Septimus with her to the Queen’s Robing Room the following morning.
Marcia is worried when Septimus does not arrive on time for his exam. As she leafs through his Prediction Practical Papers, she discovers a prediction about Septimus. Fearing the worst, she opens the Sealed section of the Library and finds a letter from Septimus among the papers of Marcellus Pye. In it, Septimus explains that he has traveled back in time and is now being kept prisoner and forced to work as Pye’s apprentice. He says he has been gone for 169 days, over six months.
Before Marcia can find Septimus and stop the prediction from happening, he follows Jenna to the Queen’s Robing Room. Queen Etheldredda demanded Jenna show Septimus a Looking Glass. He is hesitant to look at it, as he knows weird things can happen with them. Jenna pleads with him to look because the queen said that she would Reverse the Reclaime spell and he would drown at midnight.
When Septimus steps in front of the mirror, the figure of an ancient man appears and drags him through the glass. Panicked, Jenna uses a secret passage to go to her Aunt Zelda’s house for help. She finds Wolf Boy, Septimus’ friend from the army. He agrees to help Jenna find her brother.
Beetle, Septimus’ good friend, helps them by explaining they can use his dragon. Since Jenna is Spit Fyre’s navigator, she can use a special charm to temporarily order the dragon to accept her as its master. She can then charm him to Seek Septimus. Unfortunately, Beetle then falls ill with the Sicknesse that has been plaguing the city.
Meanwhile, Septimus finds himself transported back several hundred years and trapped in the care of Marcellus Pye. Pye is thrilled to have Septimus, the seventh son of a seventh son, as his apprentice. He thinks Septimus will know when his potion for eternal life is ready for consumption. Although only a few hours have passed in his own time, Septimus is stuck with Pye for six months. He misses his family and friends but is consoled as he learns more about Alchemy and medicine. He writes a letter to Marcia and slips it into Marcellus’ writings, hoping she will find it.
Jenna and Wolf Boy charm Spit Fyre and begin their search. Along the way they meet Snorri, a girl their age from the North, who has disobeyed her mother and has sailed alone to the kingdom. Snorri wants to be a trader like her dead father, Olaf. Snorri hides Jenna and Wolf Boy in her boat so Queen Etheldredda doesn’t find them. The queen believes Jenna has fled to the Marsh. Jenna and Wolf Boy leave Snorri while they fly on Spit Fyre. They pick up Nicko to help with the search, while Wolf Boy returns to the forest.
When Snorri returns to the port, her boat is impounded by Alice Nettles, the Chief Customs Officer. Some believe the Sicknesse has come from the North. Alice invites Snorri and her cat, Ullr, to stay with her in her warehouse. Ullr is charmed so at night he turns into a panther and protects the girl from harm.
Alice and Alther were sweethearts when Alther was alive, and he comes to her for help in finding a Looking Glass he believes is buried amid the junk in her warehouse. That night, Spit Fyre descends on the warehouse and tears open a box of old sheep carcasses to dine on. In the morning, the dragon tears open another box to reveal another Looking Glass, a match to the one that pulled Septimus through time. Jenna, Snorri and Nicko jump through before the adults can stop them. Spit Fyre then tries to follow them, but he shatters the portal, leaving the children stranded in time.
Jenna is mistaken for the Princess Esmeralda and promptly made a prisoner in her room by her “mother,” Queen Etheldredda. She finds Esmeralda’s diary and learns that the queen had the princess’s younger sisters killed. Jenna manages to escape and find her way to the Queen’s Room, where she then finds the secret passage to the Marsh. Broda Pye, the wife of Marcellus, is the Keeper, not Aunt Zelda. Broda is keeping the real Princess Esmeralda safe.
Jenna returns to Queen Etheldredda’s castle in time for a banquet to be held in her honor. Much to her surprise and happiness, she is served by none other than Septimus. The two escape together and find Nicko and Snorri. They discover the Looking Glass home has been destroyed.
Seeking the gateway that Marcellus had pulled him through, Septimus leads them to the chambers of the Alchemist. The children hide in a cupboard when they hear Pye and his mother, Queen Etheldredda, coming. The queen demands to drink the Tincture of Everlasting Life, even though Pye insists it is not ready.
Ullr chases the queen’s pet Aie-Aie, and the children are discovered. Snorri chases after her panther, while Jenna is whisked away by the queen. Etheldredda takes Jenna to the river with the intent of boarding the Royal Barge and then pushing her into the Whirlpool of Bleak Creek. Ullr finds them and attacks the Aie-Aie again, pushing the queen into the water. The queen sinks below the surface as Jenna watches. As the sun rises, Ullr changes back into a cat and follows Jenna to the Alchemist Chamber where she finds her brothers.
Marcellus Pye agrees to help them return home if Septimus will immediately make another Tincture that he can give to the ancient Marcellus, who still lives in their time. Pye hopes the new Tincture will restore him to his younger self.
Nicko refuses to leave until he finds Snorri, so Jenna, Septimus and Ullr return without him. Septimus keeps his promise to make a new Tincture, and he also makes a cure for the Sicknesse, using the knowledge he received from Pye. Once he returns, the first person to receive the cure is his best friend, Beetle.
The Substantial Spirit of Queen Etheldredda and her pet try to kill Jenna when she returns. Alice Nettles takes the bullet intended for Jenna, and Snorri forces the spirit of her father to restrain the queen’s ghost from pushing Jenna into a magical fire. Eventually, the queen and her pet are destroyed in the BoneFyre, and the True Crown, which had been lost, is spit from the fire as Etheldredda is consumed.