Part I opens in the late 1800s. Dr. John Watson, a British surgeon, gets injured in the Afghan War. Upon his return to London, he needs a new home and, after bumping into a former colleague, makes the acquaintance of Sherlock Holmes. The two men rent rooms together at 221B Baker Street. Since Watson is in ill health and doesn’t go out much, he focuses on Holmes. He notices that Holmes knows a great deal about a narrow range of topics but is virtually ignorant of numerous subjects. One morning, Watson makes fun of an article about the powers of observation, only to learn that Holmes wrote the article and that he works as a consulting detective.
When Scotland Yard detective Tobias Gregson asks Holmes for help in solving a mysterious death, Watson and Holmes immediately head to the scene of the crime, a vacant house in Brixton. There they meet Gregson and another detective, Lestrade. They examine the body of a dead American named Drebber. Holmes inspects the room for clues, which he uses to determine specific details about the murderer.
Watson and Holmes leave the house and visit the constable who discovered the body. They learn that a drunk man was the only bystander. Holmes deduces that this man was actually the murderer, who had come back for the wedding ring found at the scene of the crime. Hoping to catch the murderer, Holmes places an ad in the paper for the lost ring. That night, an old woman arrives to claim the ring. Holmes follows her but loses her trail, telling Watson that she was really a young man in disguise.
The next day, news of the murder fills the paper. Watson and Holmes read that Drebber had been traveling with his secretary, Stangerson, but both men disappeared. Gregson arrives at the flat and announces that he has just arrested a man for Drebber’s murder – the son of the landlady of the boardinghouse where Drebber stayed. Gregson adds that Drebber, who often drank to excess, had been thrown out of the boardinghouse for making advances on the landlady’s daughter, and the son had followed him, so naturally, he must have killed Drebber.
Lestrade then arrives with his own news. Lestrade explains that he tracked Stangerson to a hotel and found him stabbed to death in his bed. When Holmes asks about Stangerson’s possessions, Lestrade turns over a box that contains two pills. Using a sick dog as a test, Holmes demonstrates that one of the pills is benign and the other contains a deadly poison. Holmes explains that he knows the identity of the murderer but still needs to locate him. Moments later, a cab arrives for Holmes. When the driver comes upstairs, Holmes handcuffs him. The men foil the prisoner’s escape effort and plan to take him to Scotland Yard.
Part II opens in the American West in 1847. A starving man journeys across a barren desert. He stops and sets down his bundle: a young girl. They are the only survivors of a party of twenty-one immigrants, but they have now run out of food and water. After they fall asleep, expecting to die, an enormous caravan of Mormon travelers appears. The Mormons discover the man and girl, who are John Ferrier and his adopted daughter, Lucy. The Mormon leader, Brigham Young, offers Ferrier and Lucy refuge as long as they adopt their religion.
Twelve years pass, and Ferrier and Lucy have settled outside Salt Lake City, a city built and populated by the Mormons. Ferrier owns a prosperous farm. Lucy is a beautiful young woman. She and Jefferson Hope, a miner and pioneer, fall in love, but Hope has to leave town for two months. While Hope is gone, the Mormon leader announces that Lucy must wed the son of one of the Mormon Elders, but he’ll grant her one month to choose which son. Not wanting Lucy to marry a Mormon, Ferrier immediately sends a message to Hope. The same day, two young men, Drebber and Stangerson, present their case to Ferrier. They argue over who has a greater claim to Lucy, and Ferrier orders them to leave.
At the end of the month, Hope finally comes to the rescue. Ferrier and Lucy flee with him. They evade the Mormon sentries posted around Ferrier’s farm and make it to the base of the mountains, where Hope has animals waiting to carry them to safety. They soon run out of food. When Hope returns from hunting, he finds the camp empty. He finds Ferrier’s freshly dug grave nearby and realizes the Mormons have taken Lucy back to Salt Lake City. Vowing vengeance, Hope retraces his path and arrives at Salt Lake City the day after Lucy has been wed to Drebber. She dies a month later, and Hope visits her body, taking the wedding ring from her finger.
Hope retreats to the mountains and attempts to kill Drebber and Stangerson, but he fails and retreats to Nevada. When Hope returns five years later, Drebber and Stangerson have left the community. Hope travels around the country in search of the men. Many years later, he spots Drebber in Ohio. But Drebber reports Hope to the police as a dangerous man, and Hope is arrested. By the time Hope is set free, Drebber and Stangerson, who now works as Drebber’s secretary, have fled to Europe. In time, Hope catches up with them in London.
The narrative then returns to Scotland Yard, where Hope makes a statement, explaining how he killed Drebber and Stangerson for their role in Ferrier’s and Lucy’s deaths. Hope explains that he picked up a drunk Drebber the night Drebber missed his train and took him to the vacant house in Brixton, where Hope revealed his identity. Hope then forced Drebber to pick one of two pills while he swallowed the other. Drebber died of poison. Hope next tried to do the same to Stangerson in Stangerson’s hotel room, but he had to stab Stangerson in self-defense.
Soon after giving his statement and before he is tried for his crimes, Hope dies of a ruptured aneurysm. Later, Holmes explains to Watson how he made the deductions that led to Hope’s capture. In awe, Watson suggests Holmes publish his account, but the story is already in the paper with credit given to Gregson and Lestrade.