It is a concept album and a rock opera, its story following a recovering drug addict who becomes disillusioned with the corrupt society of his time and reluctantly becomes involved with a revolutionary group as an assassin of political leaders. In January 1989, it ranked at No. 34 on Kerrang! magazine's "100 Greatest Heavy Metal Albums of All Time".
During the tour promoting the 1990 album Empire, Operation: Mindcrime was performed in its entirety. The stage show featured video, animation and guest singer Pamela Moore as Sister Mary. A recording was released as Operation: Livecrime. The story was initially explored in a series of video clips for MTV in the 1989 VHS video, Video: Mindcrime.
A sequel, Operation: Mindcrime II, was released on April 4, 2006, with Ronnie James Dio taking over the role of Dr. X. The subsequent tour consisted of the band performing both Operation: Mindcrime and its sequel in their entirety, back-to-back, with actors, props, an elaborate stage set, and a video screen. The live act from that tour also portrayed Mary's death clearly for the first time. It was later released on the 2007 DVD Mindcrime at the Moore, which included a recording of Dio's only live performance of "The Chase".
In 2006, Operation: Mindcrime was re-released as a deluxe box set, containing the 2003 remaster, a live CD with the album played in its entirety at the Hammersmith Odeon on 15 November 1990, and a bonus DVD containing the 1989 Video: Mindcrime and bonus clips.
The album begins with the protagonist, Nikki, in a hospital. He lies in a near catatonic state, unable to remember anything but snippets from his past. Suddenly, Nikki's memories come flooding back in a torrent. He remembers how, as a heroinaddict and would-be political radical frustrated with contemporary society due to the economic inequality, corruption, and hypocrisy around him, he was manipulated into joining a supposed secret organization dedicated to revolution. At the head of this organization is a mysterious political and religious demagogue known only as Dr. X, who manipulates Nikki through a combination of his heroin addiction and brainwashing techniques to become an assassin.
Whenever Dr. X uses the word "mindcrime", Nikki becomes his docile puppet, a state which Dr. X uses to command Nikki to undertake any murder that the Doctor wishes. Through one of Dr. X's probable associates, a corrupt priest named Father William, Nikki is offered the services of a prostitute-turned-nun named Sister Mary. Through his friendship and growing affection toward Sister Mary, Nikki begins to question the nature of what he is doing, seeing that Dr. X has his own nefarious agenda. Dr. X takes notice and, seeing a potential threat in Mary to his cult of personality, orders Nikki to kill both her and the priest. Nikki goes to Mary's church and kills the priest, but, after confronting Mary, he fails to comply with the command to murder her. He and Mary decide to leave the organization together, and Nikki goes to Dr. X to tell him that they are out. Dr. X, however, reminds Nikki that he is an addict, and that he is the one who can provide him with his daily fix. Nikki leaves, conflicted and uncertain, and he returns to Mary only to find her dead.
Nikki cannot cope with the loss, as well as the possibility that he himself may have killed her without knowing it (whether her death occurred at his hand or at the hand of someone else such as Dr. X is left deliberately ambiguous), and he begins to succumb to insanity. He runs through the streets calling her name. The police arrive and attempt to subdue him. A gun is found on Nikki, and they take him into custody under suspicion of Mary's murder and the murders he committed for Dr. X. Suffering from an almost complete loss of memory, Nikki is put into a mental hospital, where he sees a news report on the recent spree of political homicides. This jogs his memory and returns us to the beginning where he remembers what has happened and begins to tell his story.