Average technician George Tarleton found his fate forever changed thanks to a random selection by his boss, the Scientist Supreme of A.I.M., who needed a unique, bio-engineered “living computer” in order to plumb the mysteries of the Cosmic Cube. Tarleton was subjected to hideous experiments, mutating his body into a massive-headed being possessing superhuman intelligence and extraordinary psionic powers, and the process drove him mad. Given the code-name M.O.D.O.C. ("Mobile Organism Designed Only for Computing"), Tarleton instead turned on his superiors, slaying them all and declaring himself Scientist Supreme. Moreover, he changed his name to M.O.D.O.K., with the “K” standing now for “Killing.”
Knowing only the barest of information, S.H.I.E.L.D. sent its Agent 13 to gather intelligence about A.I.M. and M.O.D.O.K., but she was captured and Captain America was then sent to the rescue. The two heroes were captured, but ultimately discovered M.O.D.O.K. when he revealed himself and tried to kill them personally. During the resultant clash, other A.I.M. agents, those opposed to M.O.D.O.K.'s leadership, turned on him and allowed Captain America and Agent 13 to escape. The submarine base destroyed, M.O.D.O.K. was believed dead, although he used his psionic abilities to save himself and soon reasserted his leadership over A.I.M.
Initially, M.O.D.O.K. turned A.I.M.’s pursuits toward acquiring technology and new recruits, running into conflict with Captain America, Doctor Doom and the Sub-Mariner, and the Hulk. During the latter confrontation, M.O.D.O.K. first used a giant robot body in a preemptive strike on the Hulk, and later he mutated Betty Ross into the Harpy to defeat him (although M.O.D.O.K. was stopped by the arrival of the Bird People.) M.O.D.O.K. used his giant body to confront Iron Man, capturing him but being defeated by the Yellow Claw.
Following this defeat, M.O.D.O.K. was deposed as leader of A.I.M., as his followers were dissatisfied with M.O.D.O.K.'s increasing preoccupation with his super-powered adversaries causing A.I.M. to largely abandon its goals for scientific breakthroughs. However, M.O.D.O.K. regained control of a West Coast faction of A.I.M. and, in alliance with Deathbird, he led A.I.M. in an attack on its East Coast division. Still, a considerable portion of the A.I.M. organization remained outside of M.O.D.O.K.'s control. M.O.D.O.K. did not realize that the members of A.I.M. whom he believed were securely under his control were secretly conspiring with the other faction of A.I.M. to destroy him. To his surprise, both A.I.M. groups joined forces and attacked him. M.O.D.O.K. retreated, soon afterwards fighting A.I.M. forces alongside the Hulk, but he finally fled after battling the Hulk himself. With M.O.D.O.K. gone, all of A.I.M. was finally reunited under new leadership.
The new leaders of A.I.M. hired the Serpent Society to assassinate M.O.D.O.K. to prevent him from posing any further threat to them. M.O.D.O.K. had escaped capture, ultimately hiding in a warehouse at a shopping mall in Newbury, New Jersey, but he was followed by both the Serpent Society and Captain America. Captain America found the weakened M.O.D.O.K. as two of the Serpents, Cottonmouth and Death Adder, were tearing away at his flesh. M.O.D.O.K. died even as Captain America was trying to help him, and the Serpents delivered his corpse back to A.I.M.
A.I.M. managed to keep M.O.D.O.K.'s body for use as a living computer, similar to his intended origin, but A.I.M. agent Yorgon Tykkio sent M.O.D.O.K. into battle against Iron Man, guiding him by remote control. At the height of battle, however, Tykkio caused M.O.D.O.K.'s headband to fire plasma that ignited underground fuel lines, causing an explosion that ultimately annihilated M.O.D.O.K.'s body.
Years later, A.I.M. once again sought the control of the Cosmic Cube, and in so doing they tore reality itself. Using the Cube, they restored M.O.D.O.K. to life, hoping that he could command the energies to fix reality. Although it was actually an Adaptoid that saved the day, M.O.D.O.K. took advantage to resume leadership of A.I.M. once more.
He returned to his preoccupation with his rivals, battling Captain America and Iron Man, but he also explored new avenues for A.I.M., such as exploring the relationship of science and magic (running afoul of Alpha Flight for reviving their member Snowbird), allying with Hydra over nanotechnology (before taken down by Citizen V and the V-Battalion), and creating a legitimate corporate front for A.I.M. as Advanced Corp. (until exposed by Iron Man.) M.O.D.O.K. was once saved by the Headmen from where he had lost himself in an extradimensional quest for additional power. In gratitude, he agreed to join them in their hopes of taking over the world, helping them do so with the help of the alien Orrgo. M.O.D.O.K. admitted, however, that this association was merely scientific, as he examined the efforts of the Headmen to better understand himself, and he and A.I.M. disassociated themselves from the Headmen before the villains were thwarted by the Defenders.
In a strange series of events, M.O.D.O.K. appeared to be hunting down and killing all A.I.M. agents responsible for his original transformation. In fact, M.O.D.O.K. had switched bodies with Damocles “the Saint” Rivas, the brother of a drug lord who developed a viral bio-weapon using M.O.D.O.K.'s DNA, and Damocles was acting on M.O.D.O.K.'s long-suppressed hatred of his form. M.O.D.O.K. had hoped to use Rivas to claim the scheme for himself, but ran afoul of the Falcon and the Anti-Cap. His defeat sent his mind back into his body, where it co-existed with Damocles. Damocles instead hoped to engage the Hulk in battle and thereby destroy M.O.D.O.K.'s form, but Captain America intervened, inspiring Damocles to use M.O.D.O.K.'s mental powers to revert the Hulk to Bruce Banner and gain his help to cure the M.O.D.O.K. virus. M.O.D.O.K. was rendered comatose, but he soon reverted to normal to once more lead A.I.M., with all traces of Damocles Rivas expunged.