Allegedly, before Earth was formed, a creator being from before time spawned the Fallen Stars, each an embodiment of one of its thoughts. On Earth, the creator made a woman, Cleito, representing the nature of reality. Cleito spawned Adam K'ad-Mon, the first Man of Lineage, and their birth site became the Nexus of Reality. Descendants of K'ad-Mon served as Nexus guardians, but over time the Men of Lineage became less concerned with this mission, until eventually one man abandoned it completely: Ted Sallis.
A biochemistry professor at Empire State University, the sheltered Sallis had no knowledge of his destiny and preferred books to people. The United States Army recruited him into "Project Sulfur," which sought a means to survive bio-chemical warfare. Sallis developed "Serum SO-2," which granted immunity to all known toxic biochemicals, but its mutagenic effects would have transformed people into monsters. Ted's friend, the free-spirited girl Sainte-Cloud, convinced him to denounce the Project, shutting it down before any serum was produced. Ted proposed to Sainte-Cloud, but she refused due to their many differences.
Returning to teaching, Sallis fell in love with one of his students, Ellen Brandt, a naïve and impassioned girl of nineteen. The two eloped following a secret affair. After their honeymoon, they visited the fortune teller Madame Swabada, who foretold a catastrophic change. Sallis was then reassigned to "Project Gladiator," a SHIELD research program based in the Florida Everglades and aimed at re-creating the lost Super Soldier Serum that had created Captain America. Working separately from his colleagues, including Dr. Wilma Calvin and Dr. Barbara Morse, Sallis modified his SO-2 formula as the basis for a new Super Soldier Serum. The subversive organization AIM wanted the serum and conspired with a bitter Ellen, whom Ted had neglected since their honeymoon.
Upon completing his new serum, Ted committed its formula to memory and burnt his records. When Ellen led Ted into an AIM ambush, he fled and injected the only existing sample of the serum into himself just before his car crashed into the swamp. He should have died, but the magical energies of the swamp combined with the serum to transform him into the hideous creature later known as the Man-Thing. His intelligence rapidly fading, he slew the AIM agents and horribly burned half of Ellen's face. Unknown to Sallis, Ellen had been pregnant.
Recovered by Project Gladiator agents, she underwent surgery that repaired her face, but it proved temporary. She gave her son up for adoption and began punishing herself for her crimes by surrendering to alcohol, drugs, and carnal indulgence. Maddened by the face she saw in the mirror, Ellen ended up in Massachusetts' Rosewell Mental Hospital, eventually restored to sanity by the enigmatic mystic Sorrow.
AIM again tried to obtain Sallis' formula, but was foiled by the Man-Thing and Ka-Zar. Man-Thing made the swamps his home and became the guardian of the Nexus of All Realities. Its magic made the swamps a focal point of bizarre activity, attracting super-beings such as Wundarr and the Molecule Man. Alongside Dakimh the Enchanter, Jennifer Kale, Howard the Duck, and Korrek the barbarian warrior of Katharta, the Man-Thing foiled a series of plots to use the Nexus to merge all realities by Thog the Netherspawn, demon lord of the realm of Sominus, and the Congress of Realities.
The Man-Thing in some sense befriended Richard Rory, Ezekiel Tork and his pet Dawg, and fought Franklin Armstrong Schist, who sought to drain the swamp in search of the Fountain of Youth; Professor Slaughter; the religious zealot Foolkiller; the Critics, afterlife agents seeking to judge the fate of suicide victim and clown Darrel Daniel; the natives of la Hacienda, home of the Fountain of Youth, whose waters nearly cured the Man-Thing and horribly mutated Schist before his death; The Glob, Yagzan, and the Cult of Entropy; the Si-Fan, alongside Shang-Chi; and the Gladiator, sent to recover Sallis' formula by Death-Stalker. Schist's wife Vivian hired Dr. Dane Gavin to capture or kill the Man-Thing; he chose the former, placing Man-Thing on display in the New York Museum of Nature History, where visitors' fears sent the Man-Thing on a berserk rampage through the city until Dr. Gavin and Schist's daughter, Carolyn, took him back to the swamp. Man-Thing later faced the manifested hate of Maybell Tork, the Demons of Liberation (embittered scarred war veterans), and the reality-altering Brian Lazarus.
Wandering into the Port Everglades, the Man-Thing was trapped on the Marietta cargo ship and caught up in a two-century-old curse involving the satyr Khordes, the immortal crew of the pirate Captain Fate, and oceanographer Dr. Maura Spinner. Maura was a reincarnation of the former captain of Fate's crew, whom Fate had traded to Khordes in exchange for his treasure. Mistaking the satyr's benevolent intent, Maura had slain Khordes, who cursed them all. After helping convince Spinner to accept her destiny by the resurrected satyr's side, Man-Thing returned to the Everglades.
The bog beast then joined old allies Korrek, Dakimh, and Jennifer Kale against the extradimensional sorcerer Klonus and warrior Mortak. In a weird twist of fate, a Man-Thing-shaped candle (created after his New York rampage) was drugged and given to Ted Sallis' former love interest Sainte-Cloud by her jilted lover Chuck, causing her to see Man-Thing hallucinations; exposed to the drug himself, a terrified Chuck badly burnt his face on the candle.
After surviving an assault from his one-time victim Jackson Hunter, the Man-Thing halted the Mad Viking's rampage. He then heeded the tortured spirit of student Edmond Windshed, taking vengeance on Edmond's former tormentors. Captured by townspeople and thrown into a sewage treatment plant, Man-Thing escaped and slew the Mad Viking, ending a violent book-burning crusade by the Viking and Olivia Selby. Now able to survive longer away from the swamp, the Man-Thing was brought by Richard Rory to Georgia, where he escaped. He fought the demon Erthold, the soul-stealing Scavenger, and Thog, whose Nightmare Boxes threatened to plunge all reality into madness until the positive wills of Ted Sallis and Steve Gerber contaminated the boxes, foiling Thog, whom Man-Thing incinerated. Alongside Ghost Rider, Morbius, and the Werewolf as the Legion of Monsters Man-Thing helped destroy the enigmatic Starseed, actually a would-be savior of humanity.
After again fighting the Molecule Man, the Man-Thing was captured along with the Glob by The Collector, who pitted them against The Hulk before they rebelled and escaped. Man-Thing later helped psychic Andrea Rodgers restore her fragmented personality, helped thwart the inane cosmic menace Bzzk'Joh, drove off D'Spayre, destroyed Jude the Entropic Man and Victorius, allied with the Cult of Entropy (narrowly missing a chance to regain his humanity), and encountered the extradimensional Micronauts.
Sallis' mind was nearly restored by Dr. Karl Oheimer's cerebral regeneration therapy for a CIA project; but the army suspected enemy involvement and tried to protect Sallis' serum by attempting to rescue Oheimer, who was slain in the process. The sentient Man-Thing slaughtered all others involved, but once back in the swamp his mind faded. Another experimental project briefly transported him to the Himalayas, where he encountered a Yeti race descended from Cro-Magnons.
The sorcerer Baron Mordo returned him to the swamp, restored Sallis's mind and used him as a pawn against Dr. Strange in a plot to destroy Earth, but Jennifer Kale helped the Man-Thing throw off Mordo's control and foil the plot, though Sallis's mind again faded.
After aiding Howard the Duck against the mad monopoly of Kong Lomerate, the Man-Thing befriended Sheriff John Daltry and Barbara Bannister, alongside whom he again met Captain Fate and opposed yet another Thog plot. This time, Sallis was cured and writer Chris Claremont took his place as the Man-Thing, destroying Thog. Dr. Strange restored Claremont, but Sallis's curse returned and proved irreversible. The Man-Thing was possessed by Unnthinnk, one of the demon coven called the Six Fingered Hand, who battled the Defenders in a massive plot to take over Earth; the Six Fingered Hand turned out to be pawns of the Hell-Lords in a scheme to use the Nexus in an aborted attempt to merge Hell and Earth.
Alongside Thor he opposed the Man-Beast and Bi-Beast, then briefly served as a pawn of the mad sorcerer Ian Fate, leading to another rampage through New York. Back in the swamps, Sallis refused an offer from the demon Eblis to become human in exchange for his mortal soul. The government's Project: Glamor developed a version of Sallis's formula, planning to attack Russia with super-soldiers, but these warriors were destroyed by the Man-Thing and others. Another Sallis serum derivation, SS-8, was used by Daemian Wainscroft, mutating his son Deke into a powerful form until being functionally lobotomized by The Punisher. Alongside the Hulk, the Man-Thing encountered a new Glob, and was later nearly destroyed by the Deviant Ereshkigal when she used the Star Brand to access the Nexus in an effort to rule all reality. Another writer with reality-warping powers used the Man-Thing to complete his final story in the last seconds of his life. Shortly thereafter, the Man-Thing was one of the Daydreamers joining Franklin Richards on a surreal journey to accept Onslaught's seeming destruction of Franklin's parents, who had actually survived in the Counter-Earth of a pocket realm created by Franklin; however, Ashema the Listener, a Celestial who would help Franklin retrieve Onslaught's victims and establish Counter-Earth as a real planet orbiting opposite Earth, obliterated the Man-Thing in order to stop him from blocking access to the pocket realm. Re-created via the combined energies of an Asgardian Norn stone and the recent breaching of the dimensional barriers, the Man-Thing's form was briefly usurped by mailroom employee Carl Schuffler, who was removed by Spider-Man using instructions from the virtually omniscient Authority.
Recent dimensional travel had shattered the Nexus of Realities, and Dr. Strange recruited Ellen Brandt to help Man-Thing restore it. In the process, the Man-Thing was possessed by K'ad-Mon, the history of the Men of Lineage was revealed, and Sallis learned that his relation with Ellen was predestined to restore his hereditary mission. Ellen, the Man-Thing, and K'ad-Mon recovered Nexus fragments from within the maddened Devil-Slayer, from Howard the Duck (despite the opposition of Mahapralaya and a revived Cult of Entropy), from Cleito herself in ancient Atlantis, and from a Nexus-created planet that Ellen had to destroy to save reality. Their efforts to restore the Nexus were opposed by the Fallen Star Mr. Termineus, the embodiment of finality, who had visited the young Ted Sallis over the years. Termineus had captured Ellen's long-lost son Job Burke and trained him as his disciple in a plot to destroy all existence. Devil-Slayer united the remaining Fallen Stars, including K'ad-Mon and Sorrow, to stop Termineus. Using the power of the final Nexus fragment, Termineus succeeded in shattering the healing Nexus, wiping out all reality. However, Sallis' nature as the Man of Lineage (combined with his love of Ellen) allowed him to briefly maintain the dream of existence; he joined forces with Job, who rebelled against his mentor, to re-imagine the creator's dream that had formed reality. All existence was restored, with Ted and Ellen inhabiting the Nexus itself, while K'ad-Mon retained control of the Man-Thing. Job returned home with his adoptive parents to live his life and prepare for his future destiny. Termineus began to plot anew to bring about the endgame, but as it was he who had involved K'ad-Mon in this struggle, he had to deal with bringing about his own failure, due to his inability to relinquish the love in his heart for his former wife, Sorrow.
Shortly thereafter, the ancient Scrier mutated one of his cabal into the Outrider to seize the Nexus. Spider-Man helped foil this plot, and Ted and Ellen drew the consciousness of the Nexus down into the Man-Thing, merging into a powerful collective being. This merged being left the earthly sphere, becoming the new Nexus, and the magic of the swamp re-formed the Man-Thing's original form, apparently instilling it with the residual memory of Sallis's consciousness. Continuing its subconscious mission to defend the swamp and Nexus, it incinerated botanist Owen Candler, creator of the Salvation Seed and the Union, which had threatened to replace humanity with plant simuloids; slew a mad scientist who tried to use the Man-Thing in experimental emotion therapy; and even opposed a universe-menacing, virtually omnipotent Thanos enhanced by the Heart of the Infinite. Eternally cursed with a monstrous form, barely aware of its past or surroundings, the Man-Thing remains the most startling slime creature of all.
The Man-Thing was recently slashed in half by Ares of the Dark Avengers and "bagged and tagged" since then however he was seen protecting the Moloids who are collecting and spiriting away the Punisher's body parts, after he is dismembered and decapitated by Daken, acting on the orders of Norman Osborn.
After Norman Osborn was deposed during the events of Seige, Man-Thing was moved to the Raft. There, Hank Pym studied it and created a device which used Man-Thing's connection to the Nexus of All Realities to enable Luke Cage's Thunderbolts to teleport anywhere in the world. He was inscribed with the 'World Song' by Satana.
Using the Nexus of All Realities, Man-Thing was able to escape the Raft and run amuk around New York City. Howard the Duck, along with She-Hulk, Nighthawk, and Frankenstein's Monster went in search of him in an attempt to stop him.
Returning to the Thunderbolts, he helped during an invasion of Chicago by absorbing the hordes of monsters sent to destroy it. This caused him to become giant-sized. Satana extracted a bulb from his old, burnt out body.