As a child, Amadeus Arkham lived with his mother, Elizabeth Arkham in a family mansion. Elizabeth was very sick, and suffered from debilitating mental illness. Eventually Amadeus murdered his mother to relieve her. He would go on to repress this memory, instead believing that she had committed suicide. Being an only child, Amadeus was the sole heir to the estate and would inherit it in his mother's will.

Because of his mother's illness, Amadeus gained a growing interest in the study of mental illness, and decided to treat the mentally ill in hopes of avoiding going through what his mother went through. He began to remodel the estate to facilitate the treatment of the mentally ill, naming the . He had convicted murderer Martin “Mad Dog” Hawkins brought from prison to his house for interview. He found Hawkins to, indeed, be mentally ill. This prompted Arkham to began to think about all of the criminals inside the system who were simply because they were sick.

Arkham married a woman named Constance and together they had a daughter, Harriet. Arkham worked at the state psychiatric hospital in Metropolis, and lived there with his family. Eventually Arkham told his family about his plans with the family estate, and they moved into the estate to oversee the renovation from the mansion to an asylum.

One evening Arkham received a phone call about the escape of Mad Dog Hawkins. The police sought his expert opinion to help aid in Hawkins's capture. Arkham gave them a brief answer, but paid them little mind. Soon after when returning from an errand, Arkham found his wife and child brutally raped and murdered, with his daughter's head severed and placed in her doll house. This was the work of Hawkins.

Arkham continued the renovation, and later saw the opening of the Elizabeth Arkham Asylum, naming it after his mother. Mad Dog Hawkins would be the Asylum's first patient. Arkham was praised for his compassion and care for taking in Hawkins despite what had happened to his family. Later Arkham would murder Hawkins during electroshock therapy, and the incident would be labeled an accident.