In an alternate version of 18th Century England scientist Victor Frankenstein discovered a method of reanimating a corpse with a soul that could think, feel and speak. After his creation was destroyed another method was used to replace the missing Soul with an artificial soul known as "Necroware." It can be upgraded like a computer programme, though the corpses are unable to speak, feel or think for themselves.
By the 19th century, the use of corpses becomes more common as Necroware is improved daily via a machine known as Charles Babbage in which Corpse Engineers have access to. John Watson, an aspiring corpse engineer, illegally creates his own Necroware and resurrects his deceased friend who he renames Friday. M, a member of British Secret service, makes a deal with Watson after catching him: either he goes to prison or becomes an agent of the British Empire. Watson chooses the latter.
In India, Watson and Friday follow former U.S. President Ulysses S. Grant and his unnamed secretary. Watson and Friday are attacked by corpse assassins but are saved by Captain Frederick Burnaby, Watson's bodyguard. Watson is tasked by M to find Alexei Fyodorovich Karamazov, a Russian corpse engineer who stole The Memorandum, which also happened to be Frankenstein's original research on reanimating a corpse with a soul. Watson is ordered to retrieve the research. Watson and Burnaby meet with Nikolai Krasotkin to act as their guide to Kabul where Karamazov is hiding.
They reach the Khyber Pass and are ambushed by upgraded corpses and rescued by Grant's secretary. Watson retrieves an advanced corpse who is able to speak its own name; Krasotkin suspects that Watson is planning to use the Memorandum to fully resurrect Friday. Watson is approached by the woman Hadaly Lilith, Grant's secretary, wishing to know if the advanced corpses contained souls, but Watson is unsure.
They locate Karamazov who explains his wish to resurrect a human as Frankenstein once did. Karamazov upgrades Nikolai, whose soul is replaced by an artificial soul while Nikolai is still alive. This kills Nikolai but creates a more intelligent corpse capable of limited thought and speech. Watson is dismayed this was what Frankenstein's original creature was and angrily berates Karamazov for not trying to improve the technology. Karamazov admits the Memorandum is in Japan and asks Watson to destroy it. Karamazov then commits suicide by having Nikolai upgrade him. Watson, Friday and Burnaby depart to Japan, leaving Nikolai, Karamazov and his corpse servants to mindlessly follow their Necroware programming forever.
A year later in Tokyo, Watson meets Yamazawa Seigo of the Imperial Japanese Army, who knows the Memorandum is held by the Osato Chemical company. Watson, along with Friday, Burnaby, and Seigo infiltrate Osato Chemical, but are attacked by advanced corpses in armour. Watson flees to find the Memorandum and has Friday analyse it, setting off a trap that sets fire to the building. The analysis causes Friday to lash out and try to speak. A strange man retrieves the Memorandum, revealing himself as Frankenstein's original creation, known as The One - still alive after 100 years and just as intelligent as a human.
Watson awakes aboard the USS Richmond heading for America. Burnaby is also on board and the feral Friday is in chains. Grant wants Watson to work for him to defeat The One, who hates humans for creating him, but Watson spends the voyage fixing Friday. Upon reaching San Francisco, The One uses the Memorandum to send out a signal that causes corpses to attack humans, including the corpse crew of the USS Richmond. During the escape, Hadaly reveals she is an artificial life form created by her "father" Thomas Edison, and she can control corpses using sound waves and desires to one day have a soul of her own. She escapes with Watson, Friday, and Burnaby while Grant is killed by an exploding corpse. At Hadaly's safe house, Watson finishes fixing Friday, making him immune to the Memorandum's signal.
The One is captured by M, who plans to turn all humans into corpses; thus ending every war. The One is taken to the Tower of London where he has his mind analysed by Charles Babbage and the preserved brain of Victor Frankenstein. A new stronger signal is sent out by M causing even more corpses to attack humans. Aboard the submarine USS Nautilus, Watson, Hadaly, Friday and Burnaby smash through the Traitors' Gate. Burnaby fights the corpse guards with Hadaly's flamethrower while the others fight their way to M. Hadaly knocks out M and uses her sound waves to suppress The One's mind, while Friday takes over Charles Babbage to stop the signal. M awakens and shoots Hadaly before being shot by Watson. Now free, The One kills M, overpowers Hadaly, and takes over Friday.
The One finally reveals his true plan, to create the bride Victor Frankenstein promised him. Having orchestrated everything, he plans to combine all the corpses primitive minds into a true human mind. Then, using the Memorandum and Charles Babbage, he will create a human soul from the knowledge inside Victor Frankenstein's brain and insert both the true mind and the human soul into Hadaly while he transfers his own soul and mind into Friday's body. As The One is on the verge of success, Burnaby damages Charles Babbage. The One is returned to his own body and Friday restarts taking over Charles Babbage, sealing The One's soul inside the Memorandum. The One tries to drag Watson in with him. Inside the Memorandum, Watson struggles until a smiling Friday helps him and The One is defeated.
Watson awakes in time to escape the collapsing building with Hadaly and an unconscious Friday. Hadaly laments over having acquired and lost her soul, though Watson assures her he likes her just the way she is. She urges him not to give up trying to resurrect Friday.
Back in the house where he resurrected Friday, Watson is seen combining the research of Karamazov with the surviving pages of the Memorandum to perform an unknown corpse upgrade on himself.
4 years later in London, Watson is seen fleeing with his new companion, Sherlock Holmes, whilst Burnaby and Hadaly, who now goes by the name Irene Adler, watch from nearby. What appears to be a fully resurrected Friday also watches from a rooftop.