Sherlock Holmes is an eccentric, highly observant consulting detective living at 221B Baker Street. He possesses an encyclopedic knowledge of crime-related subjects but remains willfully ignorant of literature and philosophy. He relies on his unique science of deduction to solve cases that baffle traditional police, finding intellectual stimulation in complex mysteries.

John Watson is a former army surgeon who recently returned to England after sustaining an injury in the Second Anglo-Afghan War. Struggling to live on his military pension, he moves into 221B Baker Street with Sherlock Holmes. He possesses a warm, conventional demeanor that contrasts with his roommate's eccentricities, and he carefully documents their investigations.

Jefferson Hope is an American frontiersman who works in various trades such as a scout, ranchman, and silver prospector. He is resourceful and deeply familiar with the rugged terrain of the American West. Driven by strong loyalties, he commits himself to protecting the people he cares about from the oppressive forces surrounding them.

Gregson is a detective at Scotland Yard tasked with solving the unusual murder of Enoch J. Drebber. He relies on traditional police methods and inductive reasoning, often competing with his peers to close cases quickly. He grudgingly seeks Holmes's assistance when a crime scene proves too perplexing.

Lestrade is another Scotland Yard detective working alongside Gregson on the Drebber case. He is quick to jump to conclusions based on surface-level evidence, such as misinterpreting the bloody writing on the wall. He views Holmes with a mixture of professional jealousy and reliance.

Enoch J. Drebber is an American traveler whose inexplicable death in London baffles the local authorities. He leaves behind few clues other than a wedding ring and the word "RACHE" scrawled in blood nearby. His personal history involves a wealthy background as the son of a prominent religious leader in Utah.

Joseph Stangerson is an American man acting as Enoch J. Drebber's secretary during their travels in Europe. Following Drebber's death, Stangerson goes missing, making him a central figure in the Scotland Yard investigation. Like Drebber, he is the son of a high-ranking official in Utah.

John Ferrier is a hardy pioneer who narrowly survives the harsh American desert by joining a passing Mormon caravan. He builds a prosperous farming estate in Utah through years of intense labor. Despite conforming outwardly to his new community, he harbors strong independent streaks and fiercely protects his adopted daughter.

Lucy is the adopted daughter of John Ferrier, who rescues her in the wilderness. She grows into a capable and beautiful young woman on her father's Utah farm. Her presence attracts significant attention from the men in her community, drawing her into intense political and romantic conflicts.

Brigham Young is the powerful and politically savvy leader of the pioneers who settle in Utah. He rules his community with absolute authority, demanding total obedience and conformity from his followers. He uses his influence to dictate the personal lives and property of those within his jurisdiction.

Madame Charpentier is the proprietor of a London boarding house where Drebber and Stangerson temporarily reside. She struggles financially and initially tolerates Drebber's poor behavior for the income, before eventually intervening to protect her family.

Alice is the daughter of Madame Charpentier. She faces aggressive harassment from the drunken Enoch J. Drebber while he stays at her mother's boarding house, prompting her brother to step in and defend her.

Arthur is a protective older brother who physically chases Enoch J. Drebber away from his family's boarding house after Drebber accosts his sister. Because he lacks an alibi for the night of the murder, the police briefly fixate on him as the killer.

Wiggins is the young leader of the Baker Street irregulars, a group of unhoused street children. Because he can travel through London without drawing attention, he acts as an effective intelligence gatherer for Sherlock Holmes.

John Rance is the police officer patrolling the Brixton Road area who first discovers Enoch J. Drebber's body in the vacant house. He provides Holmes with details about an intoxicated man he saw near the crime scene.