In the 22nd Century, Inspector Beth Lestrade believes that New London's fool-proof crime control process, called crypnosis, has been sabotaged by the criminal genius Professor James Moriarty…who has been dead for over a century! To prove her theory and catch the crook, Lestrade brings back to life the only man smart enough to have ever defeated Moriarty: Sherlock Holmes. Holmes tracks the villain, finally confronting him in the heart of the computer itself! Though the system gets back online, Moriarty manages to elude them. For now.

When New London is caught in the grip of a massive crime wave, Holmes uses his eyes and intellect to deduce that the heat of the criminal activity lies in the city's long abandoned underground. With the guidance of the street-wise Baker Street Irregulars, Holmes, Watson and Lestrade plunge into the shadowy depths to foil the plot, but lose Watson when their wild escape ends with a train crash into the Thames. Only then does Holmes realize that the robot is becoming a true friend.

On the moon, in the domed Galileo City, an old legend appears to be true when three children go missing and eerie howling can be heard echoing throughout the resort. But Sherlock Holmes suspects there is an all too human reason behind this supernatural phenomenon. His sleuthing quickly dispatches the mythical beast for what it is: trickery created by Moriarty to vacate the moon of its tourists so that its powerful defense and life support systems would be his from which to rule the earth. Though Moriarty escapes, Holmes and Lestrade cleverly foil the evil plot and save the day, the moon, and the earth!

When Lestrade corners the notorious Fenwick and his crew in an abandoned building, all she finds are innocent, mild-mannered citizens. Confounded, she calls in Sherlock Holmes to investigate. He quickly deduces that the citizens are indeed the culprits… and that Moriarty has forced a renowned plastic surgeon to use his DNA Washer device to completely alter their appearances! Using the device on himself, a disguised Holmes foils Moriarty's evil plot to switch the leaders of the free world with his own look-alike henchmen!

Someone has robbed the supposedly impenetrable safe room at Genie Tech. In the locked room – with no window or other way out - Sherlock Holmes discovers tiny scales which prove to belong to a mysterious unknown species of snake. Is this the work of the eminent herpetologist Grimsby Roylott who is trying desperately to keep the old London Zoo afloat? Or, as Watson suspects, is it the work of Forest Chapman, the proprietor of the spooky Mythological Museum where monstrous hybrid creatures are created and displayed to the delight of 22nd Century kids? Holmes looks past the obvious to discover that someone has mixed his own DNA with that of a python in order to commit the daring robberies. Holmes must then wrestle with the snake-man for his very life to win the day!

In seclusion at his remote country estate, radical anti-tech group leader Joseph Openshaw blacks out after opening a mysterious envelope containing only a cryptic note and five orange seeds. Sherlock Holmes soon discovers that the pips are poisoned and that Joseph was targeted because he – along with his brother Elias – had invented a cyber nest that could wipe out all the computers they despise forever. Though the two brothers stopped before unleashing it, Holmes now finds that Moriarty wants to use the invention to destroy New Scotland Yard's databanks and hold the world hostage. In order to get the antidote for the poison, Holmes gives Moriarty the cyber nest… but not before knowing that it is useless. All are saved and Watson helps Joseph's young son, John, learn that the true value of someone is what's in their heart.

Alexander Holder catches his own son Arthur stealing the top secret computer chip that the famous Payne computer dynasty family had entrusted him to safeguard. Why would Holder's son betray him? Did Holder's son betray him? In order to save the situation, Holmes must sift through the motives, secrets and misunderstandings of two families: not only those of Arthur, but those of the 10-year-old genius son, Helfand Payne III, and his father, Helfand Payne II, and Arthur's sister Mary and her cad of a boyfriend. Sherlock recovers the stolen chip and sorts everything out. All is made right and both families realize they have a lot more communicating to do!

The blinding flashes of disintegration haunt Watson after he witnesses Holmes and Moriarty fall from their rooftop battle into New London's laser wave sanitation grid. Despite his devastation at losing his friend, crime doesn't stop and Lestrade brings Watson to the room of a young hotshot laser tag tournament star who has been frozen solid by a freeze ray. Why? Was it because the hotshot was cheating? Or, did an opponent merely want to take him out of the competition? While investigating, Watson discovers that Holmes is still alive and in disguise! Having discovered that the marksman who froze the laser tag star was the same person who was paid by Moriarty to interfere in the rooftop battle; Holmes observes unobserved. In a gripping showdown in the laser tag arena, Holmes confronts and unmasks the culprit. Unfortunately, Holmes is not the only clever one – Moriarty is still alive, too, and still out there…somewhere.

After a break in at 10 Downing Street, it appears that the thief was only able to steal one of the African dolls from the Prime Minister's collection, and was not able to find the secret safe where Lord Devlin had hidden the top secret security plans. While Lestrade helps Greyson - who must interrupt his meeting with the famous recluse millionaire Lord Bork – to retrieve the precious doll, Holmes and Watson conduct their own investigation. After all, Holmes believes that the safe was found, that the doll is just a decoy, and that Devlin himself is somehow involved. Holmes sets a trap to catch Devlin, discovering that Moriarty has been masquerading as Lord Bork! Though Moriarty gets away, the plans are recovered before and the doll is returned safely.

At the insistence of a memo from Lestrade, the Prime Minister contacts Sherlock Holmes when the top secret virtual reality chip, called the Mazarin Chip, is stolen. But the memo is a forgery: a trap to get the Prime Minister and Holmes to Baker Street where Moriarty then descends upon them, trapping Holmes in a virtual prison and kidnapping the Prime Minister. Holmes must escape his virtual prison and discover where Moriarty really is before he is able to create 10 Downing Street with the Mazarin Chip and access all the Prime Minister's power. Holmes is able to free himself then the Prime Minister, but must use Moriarty's own methods against him to retrieve the chip. Holmes saves the day…but Moriarty gets away.

After draining the Sussex County Holocomputer System of every drop of data, a cackling vampire-like creature locks himself inside the vault at London First Bank. Beth corners it and blasts open the vault with ionic canon…only to find nothing there! Byte-sucking fiend or computer generated count? Holmes must call on the Irregulars to help track the alleged vampire to its lair…where Moriarty appears, trapping Holmes and the gang. But Beth foils Moriarty's attempt to make the vampire his ally, while Holmes reveals the vampire to be the well-meaning 10-year-old girl she is. Miss Amanda Wheelright, a famous computer hacker among the underage genius set, had stumbled onto Moriarty's data theft scheme and had created the vampire to foil him. Moriarty is vanquished, but Beth must still explain all the destruction she caused at the bank!

Christmas in New London finds the whole city gone mad for the hot toy to have: the Blue Carbuncle, a troll-like doll that can mimic a real person and appear to communicate. Holmes inadvertently hurts Watson's feelings when he expresses his disgust at the modern world's obsession for machines. But when Beth brings him one of the coveted dolls after recovering it from a mugging, Holmes quickly realizes that this doll is much more sophisticated than those in the advertisements. This doll has a special artificial life computer chip that bestows sentient thought to robots! The maker of the valuable chip hid it in the doll when he realized Professor Moriarty was closing in, but then lost sight of the doll when it was carted off with dozens exactly like it! Both Moriarty and the chip's creator have been searching for it since. Holmes uses the doll itself to bait Moriarty and to discover the true maker of this very special doll, learning the true nature of friendship in the process.

Holmes and Lestrade uncover an elaborate plot which involves red-headed crooks swapping paintings at the National Art Gallery for forgeries…and which employs a crowd of innocent red-headed men to screen their getaway. Who are all these red-heads? The League's employer is none other than Professor Moriarty who is planning to release a chemical (via the forgeries) at a gala to be held that night at the National Art Gallery. By rendering the wealthiest people in Britain helpless, Moriarty can steal their possessions and hold the nation's wealthiest recluse hostage. But Holmes foils the plan, the real art work is replaced, and no one is hurt. And newest League member and fish-and-chip shop owner Carter Wilson gets a new piece of artwork for his own Red-headed League!