Inspired by the works of H. P. Lovecraft, and in particular his fictional city of Arkham, Massachusetts,[2][3] the asylum was introduced by Dennis O'Neil and Irv Novick and first appeared in Batman #258 (October 1974); much of its history was established by Len Wein during the 1980s.

Arkham Asylum has a poor security record and high recidivism rate, at least with regard to the high-profile cases—patients, such as the Joker, are frequently shown escaping at will—and those who are considered to no longer be mentally unwell and discharged tend to re-offend.

Later, serial killer Martin Hawkins, also known as Mad Dog, kills Amadeus' wife and daughter.

In Alan Moore's run in Swamp Thing the Floronic Man is detained there and in The Sandman by Neil Gaiman, Doctor Destiny escapes the asylum to wreak havoc on both the real and dream worlds.

A Serious House on Serious Earth has been critically acclaimed, having been called "one of the finest superhero books to ever grace a bookshelf.