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When nanites - tiny, self-replicating robotic spies - are discovered in the Warehouse, Claudia deduces that Sykes planted them in order to hack into a file called Atlas 66. Myka is itching to get into the field to neutralize Sykes and demands that Jane reveal the contents of this heretofore Regent-only file, but Jane puts the kibosh on the inquest - the Regents have a plan in motion and all agents are to stay put.
But Myka, Pete and Claudia can't sit still while someone targets everything and everyone they love. A clue from Claudia's surreptitious decryption of Atlas 66 sends Pete and Myka to a nearby high school, where they discover a woman who looks exactly like H.G. Wells. It's soon clear that this woman has none of the malice or cunning of H.G., but while Pete and Myka try to deduce what Sykes would want with this human anomaly, Sykes's henchman arrives. Myka secrets H.G., who says her name is Emily Lake, away to safety while Pete engages Sykes's right hand man in a battle that ends with the villain plummeting to his death from a fifth-story balcony.
But when Pete reunites with Myka and her charge, the women are in the sights of their former partner, Jinks, who is soon joined by the recently deceased henchman. While Pete and Myka try to wrap their brains around the devilish pairing of their onetime friend with a possibly immortal murderer, Jinks blasts them both with a Tesla and smuggles H.G. to Sykes's lair.
Though Artie's ready to rip his agents to smithereens for disobeying him, Jane reminds them that there's work to do. She explains that the hologram of H.G. that helped them with a previous case was separated from the body of H.G. - the Regents wanted to give the brilliant woman a chance at a new life, so they created two women - one physical, one metaphysical - with the help of an artifact called the Janus Coin. Once Sykes realizes that Emily Lake possesses none of the knowledge or skills of Wells, he will surely seek the Coin.
Once they have it in their possession, Pete proposes a radical plan to save the Warehouse: Since Sykes needs the Coin for his endgame, the Coin must be destroyed. Myka protests, as destroying the Coin means destroying H.G. But when Claudia summons H.G.'s consciousness, the literary genius insists that Pete go forward with his plan.
But Jinks and his cohort halt Pete in his tracks. They steal the Coin, but not before Jinks slips Claudia Sykes's whereabouts - Jinks has been undercover the whole time. Jane confesses that this was the plan she alluded to, and the agents rush to the secret location to save their friends, and possibly the world.
An empty airplane hangar rings with desolation and defeat: Sykes has escaped. But the loss of the Coin and H.G. feels small when Claudia discovers Jinks, lying murdered in the emptiness of Sykes's hideout.
The accidental discovery of a microchip launches Claudia from her heaviness into action mode. Inserting the chip into a flash drive, the team discovers a video from Jinks telling them that Sykes is planning a trip to Hong Kong, the site of Warehouse 7 as well as of the Regent Sanctum.
Sykes's trail leads Pete and Myka under the streets of Hong Kong to a deeply buried lair where Sykes has his computer hacker, Tyler, strapped into a chair with an axe above it and Wells, controlled by Sykes via Cecil B. DeMille's riding crop, pointing a gun at the young man's head. It seems the key to unlocking the Regent Sanctum lies in winning a game of chess played against a bewitched chess set. But should the human player make the wrong move, his head will be split open by the axe above.
Wells pleads with Sykes to release Tyler and give up his crusade, but Sykes does not relent and Tyler loses his life. Upon discovering the two agents, Sykes turns his weaponry (namely, Wells) on them and forces Myka to have a go at the deadly game. With the stakes raised, Wells is able to remember words of wisdom from her mentor, the man who invented the chess lock: "Change the rules." Wells instructs Myka to make a move with her pawn that defies the rules. With a shudder, the axe disappears and the wall next to them transforms into a portal leading to Warehouse 13. Sykes uses Pete as his new puppet and the two men pass through the portal, which Sykes closes before Wells and Myka can follow.
Artie and Jane are trapped inside by means of Jane's shackle, which raised an impenetrable field when it felt the threat posed by Sykes's henchman, Marcus, who aimed an artifact cannon at the Warehouse. Since Marcus is still alive and Sykes is entering the Warehouse, the threat is active, meaning no one is getting out anytime soon. Sykes turns son against mother and forces Jane to retrieve the Collodi Bracelet. The villain dons the manacle and his eyes deepen to an inky black. He stands, his full faculty restored, and forces Pete to turn the gun on himself. Jane is in agony and begs that her life be taken, instead, but Sykes is pitiless.
But Wells and Myka have reopened the portal and manage to get a lucky Tesla shot in before an artifact ensnares them in its ropy tangles. Sykes quickly recovers, but the crop is lost. He continues his pursuit of Jane, who flees through the reopened portal and as Sykes runs after her, Pete closes the portal, trapping Sykes in solid rock.
Pete calls his mother via Farnsworth to make sure she's okay, then returns to Artie, Myka and Wells, surprising the latter with a heartfelt hug. They then contact the inn, where Claudia tells them that Marcus is dead thanks to the combined efforts of herself and Mrs. Frederick. An artifact - a metronome - had been keeping the man alive and when Claudia stopped its rhythm, Marcus's heart stopped with it. Against Mrs. Frederick's wishes, Claudia intends to use this same metronome to bring back Jinks.
If the threats to the Warehouse have been eliminated, why hasn't the barrier disappeared? Some threat must still be present in the Warehouse. Artie pieces together clues from Sykes's words and discovers an atomic bomb in the dead man's wheelchair. As he, Myka and Pete attempt to disarm it, Wells quietly rigs some wires and extends the Warehouse's protective field around her three compatriots. She wasn't able to include herself in the bubble - it had to be created from outside - but she is grateful to know that her friends, and the rest of the world, will be safe from the atomic blast.
As flames rip through the aisles, Myka sends a forlorn look to her lost-and-found friend, and hundreds of years of artifacts are destroyed. The blast clears and Pete voices his sense of defeat after such a long battle.
Pete didn't count on Artie, who reveals a mysterious pocket watch, and utters a sentence that hints that thoug the battle may seem lost, it is not yet over.