As a career test pilot and astronaut, Col. John Jameson was, according to his father J. Jonah, "made of the stuff of heroes", unlike masked menaces such as Spider-Man. However, Spider-Man has saved his son's life on numerous occasions. During his first mission orbiting Earth, Spider-Man replaced a guidance module in Col. Jameson's plummeting space capsule. In a subsequent mission in space, Jameson contacted spores from Jupiter that endowed him with superhuman strength, increased his size, and made him act more aggressively. NASA gave him a special suit from Tony Stark's lab to keep his strength in check. When it appeared that Spider-Man was responsible for a bank robbery, John was persuaded by his father to become a public hero by apprehending him. Spider-Man had the upper hand, but John sought a rematch. This time, Spider-Man neutralized the spores with a dose of high-voltage electricity, returning John to normal.
Later, Jameson was sent to the moon to collect rock samples on a top-secret mission and stumbled upon a glittering red gemstone. Once his mission was complete, he had a strange urge to obtain the gemstone from quarantine and have it made into a pendant, which he wore around his neck. The stone reacted to the moonlight on the first night of the next full moon, transforming Jameson into a savage lupine creature. The gem was actually the Godstone, the crystallized power and essence of Stargod, an ancient ruler from a dimension called Other Realm. When Stargod was dying he opened a portal to Earth's moon and channeled his energy into the jewel, which had landed there millennia before following the destruction of the collection of power gems known as the Lifestone Tree. Ancient prophecies foretold that in evil times, Stargod would be reborn to save the people of Other Realm. The energies of the Godstone transformed Jameson into the form of the Stargod, but the radiation that leaked through the portal to Other Realm was so weak that the change was only partial. Whenever the moon shone upon the Godstone, Jameson gained the form, strength, and primal fury of Stargod, but lacked his wisdom and power.
Jameson fought the transformations for months. As the Man-Wolf, he instinctively sought out and seemingly attacked his father, who was quick to suspect the creature was partnered with Spider-Man. When Jonah recognized the pendant around the Man-Wolf's neck, he knew the creature was his son. However, he could not cure him by removing the pendant, since it had grafted itself onto his skin. In a subsequent battle with the Man-Wolf, Spider-Man tore the stone from his neck and threw it into the Hudson River. The wound took months to heal, but Jameson was cured.
Unfortunately, the artificial vampire Michael Morbius recovered the stone and reverted Jameson into the Man-Wolf again, hoping to use the beast in a scheme to cure himself of his affliction. Spider-Man thwarted the effort, but both Morbius and Jameson escaped. Once again, the Man-Wolf ran rampant monthly. The police assigned special investigator Simon Stroud to the case of the Man-Wolf. Jameson fled New York to Georgia where he became entangled in a fight between S.H.I.E.L.D. and the Hate-Monger (a clone of Adolph Hitler). Nick Fury, director of S.H.I.E.L.D., escorted Jameson back to NASA, where he had been absent without leave. NASA offered to drop the charges if Jameson agreed to perform a secret mission to investigate the communication breakdown with an orbiting space station. At the station, Jameson began his journey to discover the other-dimensional origin of his powers. He journeyed with three humanoids from Other Realm through the portal on the moon into their dimension. There, he was fully transformed into the essence of Stargod, this time maintaining his personality and intelligence. Fulfilling the prophecies, Jameson donned the costume and wielded the weapons of Stargod, ultimately managing to access his full power and help the "Realmites" defeat the tyrant Arisen Tyrk .
Using the Godstone, Jameson teleported back to Earth. Once again he found himself afflicted with lycanthropy as the stone bored itself into his throat. This time, the stone was slowly poisoning him. In hopes of a future cure, John's body was cryogenically frozen, but Jameson was thawed and mentally controlled by the dying scientist Spencer Smythe in an attempt to get revenge on Jonah and Spider-Man. Atop the Brooklyn Bridge with Spider-Man and his father, Man-Wolf reverted back to human. Smythe remotely caused John to fall backwards in agony off the bridge only to disappear. The Godstone had dimensionally teleported him away. Once again he became the Stargod and, with She-Hulk and Hellcat, saved Other Realm from gravitational collapse. Although he enjoyed being the Stargod, Jameson decided to return to Earth, losing his memory of Other Realm. Reunited with his father, he and Spider-Man sought Dr. Curt Connors to administer a biomagnetic treatment that caused John's body to reject the Godstone. With the stone crumbled into powder, he ceased transforming into the Man-Wolf. John broke up with his fiancée Kristine Saunders and spent some time at the Sherwood Nursing Home sanitarium to mentally recover from all his life's ordeals. There, before his father's second marriage, he was kidnapped by the Scorpion, but was rescued by Spider-Man.
For a time, Captain America hired Jameson to serve as pilot of his personal Quinjet, Freedom's Flight, as well as his van. While aboard the Freedom's Flight, Jameson's alias was "Skywolf"; while aboard the van, his alias was "Vanwolf". Jameson assisted Captain America during the "Bloodstone Hunt", and in his attempts to combat the drug trade during a turf war between the Kingpin and the Red Skull. At one point, Jameson was hypnotized with other members of the Avengers support crew by Mother Night and Minister Blood, and was forced to assist them in an attempt on the Avengers' lives, but the Avengers managed to halt him. Eventually he was contacted by the villain Dredmund Druid. Jameson attempted to defeat Dredmund himself, but was overpowered and temporarily transformed into a werewolf that greatly resembled his Man-Wolf form. Dredmund reassembled the Godstone and attempted to use it, but was defeated by Captain America; the stone was destroyed again. John was attracted to Captain America's girlfriend Diamondback and left his employment in shame after trying to steal a kiss.
After a time as a freelance monster-hunter, he served as security chief at the Ravencroft Institute, where he began a romantic relationship with the director, Dr. Ashley Kafka. After several problems with superpowered criminally insane inmates including Carnage, the Institute was temporarily shut down. Kafka thought she was close to healing the Chameleon of his mental illness, but was duped by the villain, enabling him to escape and kidnap her, John, and Spider-Man. With this final breach of security, Senator Roeberg fired Jameson and Kafka, hiring Dr. Leonard Samson as the new director of Ravencroft. Shortly thereafter, Mad Jack (Daniel Berkhart) implanted a command in Jameson's mind to smother his hospitalized father with a pillow, causing John to act wolf-like, though in human form. Kafka used hypnosis to undo the effects, transforming him temporarily into the Man-Wolf despite the absence of the Godstone. Residual affects of the Godstone are apparently permanently a part of Jameson. He and Kafka broke up sometime thereafter.
John hopes to someday return to a more adventurous life. For now he is living simply as a social worker. He recently expressed some romantic interest in She-Hulk, and gave her his Jupiter suit (after a few modifications by Reed Richards) to help her manage her out-of-control strength. Currently, to end a crusade to discover Spider-Man's identity, John's father has been tricked by Peter Parker into believing his son is secretly Spider-Man.