When he was ten, Holmes was terrified of the skeleton in the doctor’s office, and two older classmates knew this. One day, they grabbed him and forced him into the empty office, pushing him closer and closer to the outstretched arms of the skeleton until he was face to face with its creepy grin. Some say this ignited either anger or pure fascination for Holmes, mapping out his murderous future.

In Chicago, Holmes secured a job at a local pharmacy. When the owner passed away, leaving his wife to manage the store, Holmes convinced her to sell it to him. Shortly afterward, the widow mysteriously disappeared and was never seen again. Holmes claimed she had moved to California, but this was never verified.

With his new business established, Holmes purchased the lot across the street at 63rd and Wallace Streets, a site that would later become infamous as The Murder Castle.

In 1893, Chicago was given the honor of hosting the World’s Fair, a cultural and social event to celebrate the 400th anniversary of Columbus’ discovery of America (The World's Columbian Exposition). The event was scheduled from May to October, and attracted millions of people from all over the world. When Holmes heard that the World’s Fair was coming to Chicago, he looked at it as an opportunity. He knew many visitors would be searching for lodging near the fair and believed many of them would be women whom he could easily seduce into staying at his hotel. After being lured into the hotel, many of these out-of-town visitors would never be seen again.

Holmes hired and fired several construction crews to ensure no one fully understood his plans—he was building what would later be called the "Murder Castle." After its completion in 1891, he placed ads offering jobs to young women and rented rooms to visitors, while also posing as a wealthy bachelor seeking a wife.

Almost everything was done on credit, as Holmes rarely paid upfront, solidifying his reputation as a conman. He would hire workers for small tasks—one to build a wall in one room, another for a different room—then fire them, often claiming the work was substandard to avoid payment. The Castle’s design, much like the famous Winchester House, was filled with doors opening to brick walls, stairways leading nowhere, and hallways meant to disorient tenants, making them easy prey.

The building was a nightmarish labyrinth with over 100 windowless rooms, dead-end staircases, and hidden trapdoors and chutes for moving bodies undetected. Some rooms were equipped with gas lines to asphyxiate victims, while soundproof chambers concealed their screams. The twisted layout made escape nearly impossible.

The first floor housed shops, while the upper levels contained Holmes' office and more than 100 living quarters. These rooms were often soundproof and fitted with gas lines, allowing Holmes to kill at will.

All of Holmes’s employees, hotel guests, fiancées, and wives were required to have life insurance policies. Holmes paid the premiums as long as he was listed as the beneficiary. Most of his fiancées and wives suddenly disappeared, as did many of his employees and guests. People in the neighborhood eventually reported seeing many women enter the Castle, but never saw them leave.

Benjamin Pitezel became one of Holmes’s most notable victims. Initially Holmes’s business partner, Pitezel was drawn into a life insurance scam that ultimately cost him his life.

Holmes convinced Pitezel to fake his own death for a $10,000 insurance payout. Instead, Holmes murdered Pitezel and used a corpse to claim the money. He then killed three of Pitezel's children.

Holmes had become a surgeon upon college graduation and it is believed that throughout his university career, he made a habit of stealing corpses and collecting on fabricated life insurance policies. He had practiced surgery on animals as a child, and it is believed that he also used the stolen bodies to perform deranged experiment.

The Murder Castle was a nightmarish maze of soundproof rooms, hidden chutes, and deadly traps. Many rooms had chutes leading directly to the basement, where Holmes had vats of acid, quicklime, and a crematorium for disposing of bodies. He also sold skeletons to medical schools after stripping the flesh from his victims.

Secret chutes connected the upper floors to the basement, allowing Holmes to quickly transport bodies for disposal. The basement also housed holding cells where victims were sometimes kept before their deaths.

Throughout the Castle, there were movable walls, hinged dividers, and hidden, airless cells. Some rooms had up to five doors, while others had none. Iron-encased walls muffled sound, and below his apartment, a trapdoor in the bathroom led to a stairway and a roomless cell. A nearby chute funneled directly to the basement.

One infamous room had gas fittings, where Holmes would lock his victims inside, turn on a light in an adjacent room, and watch as they suffocated. A complex alarm system was connected to doors and staircases, with a bell in Holmes's bedroom that alerted him whenever someone entered the hallway or went downstairs.

Trapdoors, peepholes, and chutes led to the basement, which Holmes used as a laboratory equipped with a dissecting table, stretching rack, and crematory. He would send bodies down the chute, dissect them, and sell the skeletons to medical schools, or dispose of them by cremation or in pits of acid.

After the completion of the Murder Castle, Holmes began luring victims—mostly women—inside to meet grisly fates. His first known victims were his mistress, Julia Conner, and her daughter, Pearl. In 1891, Julia became pregnant by Holmes and demanded marriage. He agreed, but only if she allowed him to perform an abortion. On Christmas Eve 1891, both Julia and Pearl disappeared without a trace.

The Murder Castle was outfitted with a sophisticated alarm system, intricately linked to doors and sections of the staircases. Anytime someone entered a hallway or descended the stairs, a buzzer in Holmes’s bedroom would sound. While this might seem harmless, in the hands of a serial killer, it became a deadly tool. The system allowed Holmes to monitor the movements of guests roaming the halls at night, ensuring he was alerted whenever someone left their room.

But it didn’t stop there. The alarms also ensured that even if someone managed to escape one of the hidden torture chambers scattered throughout the second floor, they couldn’t leave undetected. In essence, Holmes had created a primitive version of a modern security system—not for protection, but to ensure he could kill with maximum efficiency.

While most of Holmes's devices were designed to kill his victims from a distance, one room in the Murder Castle catered to his more hands-on approach. Some victims met their fate in the "Secret Hanging Chamber," where they were hanged. Holmes, who apparently took pleasure in strangulation, carried out his grim work. After stalking his prey through hidden passageways, he’d render them unconscious with chloroform, then drag them to this concealed chamber to finish the job.

In October 1895, Holmes finally faced trial for the murder of Benjamin Pitezel. He was convicted and sentenced to death by hanging, which was carried out at Moyamensing Prison on May 7, 1896. In a twist of fate, Holmes’s neck didn’t break during the execution. He writhed in agony for over 15 minutes before being declared dead at 10:57 AM.

When investigators combed through the castle following Holmes's arrest, one of the most chilling discoveries was a network of gas pipes concealed within the walls and floors. These pipes were linked to valves in Holmes’s private quarters, allowing him to release gas into the rooms of his unsuspecting, sleeping victims at will, slowly suffocating them without a sound. Even those close to him couldn’t be sure they wouldn’t meet the same fate—Chicago authorities suspected this was how he killed his mistress and bookkeeper, Julia Conner.

Holmes murdered his victims and skillfully used his medical knowledge to profit by selling their organs on the black market, while also cashing in by selling their skeletons to medical schools. Whatever remained of their bodies was dissolved in acid or burned away in the crematorium, leaving no trace behind.

Holmes had a massive vault installed in the castle, cleverly embedding it within the structure during construction. In 1892, he lured his second mistress, Emeline Cigrande, into the vault under the pretense of retrieving some papers for him. She complied, unaware of his true intentions, and once inside, he sealed the airtight door, locking her in. Calmly, he returned to his desk, listening to her desperate cries for help, which gradually faded as she suffocated. After her death, Holmes wasted no time, selling her clean skeleton to a medical school shortly thereafter.

Holmes varied in his victimology and methods. His victims were often employees, lovers, or hotel guests. Some were locked in soundproof rooms equipped with gas lines, allowing Holmes to asphyxiate them. Some victims were trapped in a soundproof bank vault and left to suffocate, while others were taken to a hidden room sealed with solid bricks, accessible only through a trapdoor in the ceiling, where they were left to die of starvation and dehydration.

After their deaths, Holmes would transport the bodies through a metal chute or dummy elevator to the basement, where most were dissected, stripped of flesh, turned into skeleton models, and sold to medical schools. Alternatively, he disposed of bodies in lime pits, incinerated them, or used corrosive acid, poison, and even a stretching rack.

His crimes are some of the most lurid in American history. He outfitted his "murder castle" in Chicago with secret chutes, stairways that led to nowhere, rooms with locks that would seal a person inside, with no access to keys or how to get out.

Holmes was an avid reader and, as a youth, would spend hours immersed in the writings of Edgar Allan Poe, one of his favorite authors. Interestingly, Poe was once imprisoned at Philadelphia’s Moyamensing Prison, the same prison where Holmes was eventually executed. In 1849, Poe reportedly became drunk and suicidal one night. He was arrested for public drunkenness, spent the night in prison, and was released the following day.