Chapter 3 begins in August 1886, when H.H. Holmes takes a train to Englewood, Illinois, a community near Jackson Park, future site of the 1893 Chicago World's Fair. Holmes enters E. S. Holton Drugs and convinces store owner Mrs. Holton to hire him. In serious need of help because of her husband's medical condition, Mrs. Holton becomes employer to the doctor, pharmacist, and unsuspecting serial killer.
The plot flashes back to the childhood of Mudgett (eventually known as H.H. Holmes) in Gilmanton, New Hampshire, and traces Mudgett's life until his arrival in Chicago. Like most serial killers, Mudgett shows signs in his childhood that he's going to be a killer, including a haunting encounter with a doctor's office and the "accidental" death of his childhood friend, an event at which Mudgett is present. In his first career, Mudgett teaches in New Hampshire, where he marries Clara A. Lovering and eventually leaves her, although he never legally divorces her. He then goes to medical school in Michigan and graduates in 1884. After medical school, he moves around from city to city until he lands in Chicago.
The action moves back to Holmes and his new work at E.S. Holton Drugs. After the death of Mr. Holton, Holmes offers to buy the business from Mrs. Holton and let her live upstairs. She agrees, and Holmes takes out a loan against the store to pay for this business venture. He even changes the name of the store. Soon after, Mrs. Holton mysteriously disappears. Holmes makes up a story about her visiting out-of-state relatives to those who inquire about her whereabouts.
In Chapter 3, the reader becomes more acquainted with Holmes, antagonist and a main character in the novel. The author immediately creates distrust of Holmes by using flashback into Holmes's mysterious and questionable past. Erik Larson characterizes Holmes as a ladies' man and smooth-talker, a man whose looks and charm women find irresistible. The reader, already knowing Holmes is a serial killer, recognizes that these skills will likely serve the murderer well later in the novel when he uses his charms to lure his victims.
Larson uses allusions to help develop Holmes's character. Larson makes allusions to Chicago's Union Stockyards and Upton Sinclair's The Jungle. The Union Stockyards is the meatpacking district in Chicago during this time. To research his writing of The Jungle, Sinclair worked in Chicago at the stockyards. In The Jungle, Sinclair gives a gruesome account of the meatpacking industry as corrupt, unsanitary, and diseased. By alluding to the stockyards and to Sinclair's novel, Larson paints a similar mental picture of H.H. Holmes. These allusions also serve as foreshadowing for the horrific deaths Holmes's victims endure and the corruption he employs to serve his purposes.