Professor James Moriarty is a fictional character and the archenemy of the detective Sherlock Holmes in the fiction of Sir Arthur Conan Doyle. Moriarty is a criminal mastermind, described by Holmes as The Napoleon of Crime. Doyle lifted the phrase from a real Scotland Yard inspector who was referring to Adam Worth, one of the real life models of Moriarty. The character of Moriarty as Holmes' greatest enemy was introduced primarily as a narrative device to enable Conan Doyle to kill off Sherlock Holmes, and only featured directly in two of the Sherlock Holmes stories. However, in more recent derivative work he is often given a greater prominence and treated as Holmes’ primary antagonist.

Although Moriarty appeared in only two of the 60 Sherlock Holmes tales by Conan Doyle, Holmes’ attitude to him has gained him the popular impression of being Holmes’ arch-nemesis . as The Final Problem clearly states: “Holmes spent months in a private war against Moriarty’s criminal operations” . and he has been frequently used in later stories by other authors, parodies, and in other media. In the Doyle stories, narrated by Holmes’ assistant Doctor Watson, Watson never meets Moriarty (only getting distant glimpses of him in The Final Problem), and relies upon Holmes to relate accounts of the detective's battle with the criminal.

The model which Conan Doyle himself mentions (through Sherlock Holmes) in The Valley of Fear is the London arch-criminal of the 18th century, Jonathan Wild. He mentions this when seeking to compare Moriarty to a real-world character that Inspector Alec MacDonald might know, but it is in vain as MacDonald is not so well read as Holmes.

It is averred the surviving Jesuit priests at Stonyhurst instantly recognized the physical description of Moriarty as that of the Reverend Thomas Kay, S.J., Prefect of Discipline, under whose aegis Doyle came as a wayward pupil. According to this hypothesis, Doyle as a private joke has Inspector MacDonald describe Moriarty: "He’d have made a grand meenister with his thin face and grey hair and his solemn-like way of talking."

Finally, Conan Doyle is known to have used his former school, Stonyhurst College, as inspiration for details of the Holmes series; among his contemporaries at the school were two boys named Moriarty.