Despero has appeared in both comic books and other DC Comics-related products such as animated television series and feature films, trading cards, and video games.

[2] Despero first appeared in Justice League of America #1 (October 1960) and writer Mike Conroy noted: "It was the first of several run-ins the would-be universe conqueror would have with the superteam".

Despero eventually reappeared whole in the graphic novel JLA/JSA: Virtue and Vice (December 2002), and featured in the "Crisis of Conscience" storyline in JLA #115–119 (September– November 2005), Superman/Batman #33 (March 2007), and Trinity #4 (June 2008).

[4] The rebels make contact with the Justice League of America with JLA member Flash accepting Despero's challenge after he places the rest of the group in a hypnotic trance.

[5] Despero found out about this by reading the mind of one of the rebels he had tracked down and teleported, though her father and Flash were protected by the dimensional traveller's 'blue glow'.

The JLA are able to escape all the dangers on the worlds and return to Earth using a dimensional traveler one of Despero's henchmen possesses after the Flash defeats him.

[7] Despero is thwarted again when the Justice League intervene in his intergalactic plans of conquest,[8] save the Martian Manhunter who is being forced to play in a life and death chess match.

The villain quickly defeats the Manhunter, although fellow Justice League member Guy Gardner arrives and hurls Despero away.

[16] The villain makes a second attempt to return to a corporeal state, attacking a circus and luring out teen heroes Young Justice.

Although Despero takes mental control of several members of the League, he is eventually stopped by Green Lantern and imprisoned on the planet Oa.

[20] Despero returned in his original human form when plucked from the timestream by Mister Mind, and is convinced to join a group called "The Time Stealers".

Booster Gold, Rip Hunter and Justice League International eventually undo the change and restore the original universe.

[21] Despero briefly allied with villains Morgaine le Fey and Enigma and became god-like until stopped by the combined efforts of Superman, Batman, and Wonder Woman.

[26] In Forever Evil, Despero appears as a member of the Secret Society of Super Villains when the Crime Syndicate invade the main universe.

[27][28] Despero is an alien from the planet Kalanor, and in addition to a genius intellect possesses a third eye on his forehead capable of mind control, illusions, telekinesis, and telepathy.