First series (Dark Horse, 1991–1995)

In 1955, an explosion in Antarctica draws the attention of a group of scientists. There they discover dozens of charred bodies, some of which do not appear to be human. Among them is a creature in a mechanical exoskeleton, named Sathanas, who kills all but one of the scientists, whom Sathanas uses to meet Senator Aldus Hilltop. Together, with Sathanas' existence kept secret, the three construct "Project Next Men", whose goal is to create superhumans. The project used babies who were given up for adoption by single mothers. Due to Hilltop's racial concerns, all of the mothers were white. The children were experimented on and grew to maturity in a lab while in their minds they experienced an idyllic virtual-reality world.

Eventually five of these "Next Men" manage to escape from confinement, but once free, they find that their powers are very greatly enhanced from how they were in their virtual world. The Next Men are:

• Nathan, whose mutated eyes allow him to see a wide spectrum of light. Team leader.
• Jasmine, a young super-acrobat. Nathan nicknames her "Jazz".
• Jack, who is super-strong but cannot control his strength.
• Bethany, who is invulnerable to harm to the point of having razor-sharp hair, but who loses physical sensation and whose skin bleaches white.
• Danny, who can run at superhuman speeds.

After escaping from the Project, the Next Men have a number of interactions with outsiders, including a previous escapee who is deformed. Eventually, they are taken in by a US government agent, Tony Murcheson, who works for an individual known as Control. Murcheson works as their handler from that point in the series, intervening when she can and offering a reality check to her naive charges. During their first official mission in Russia, the Next Men are captured. Jasmine, afraid they will be killed, seeks solace in the arms of teammate Nathan, and the two unknowingly conceive a child. Meanwhile, Danny, the youngest member of the team who was not allowed to go on the mission, goes on a quest to find his birth mother. Reunited with her, she reveals the identity of his father: Aldus Hilltop. Afterward, his new half-sister convinces Danny to take her away from their abusive mother. The two run off to New York City, where Danny hopes to meet his hero, the fictional comic-book character, Action Maxx. He finds instead the character's publisher, who decides to exploit Danny and the other Next Men for a new comic-book series, once Danny convinces him that his claim of having superpowers is real. This brings the Next Men to the attention of law-enforcement authorities investigating the damage left in the wake of the Next Men's escape from the Project. After a publicity stunt for their upcoming comic book, the Next Men are arrested, tried and convicted on multiple counts of murder. Before they can be sent to prison, Murcheson helps the Next Men escape, and the team lives for a time in a subterranean community of the homeless and disenfranchised.

During his time at the comic-book publisher, Danny is befriended by a young woman named Sandy who is in charge of babysitting him. The two eventually have sex, and the woman goes on to develop reality-altering powers. These powers cause her to go crazy and attempt to remake the island of Manhattan. Once she is stopped by the Next Men, it is discovered that the powers which they have are sexually contagious; anyone who has sex with one of the Next Men will develop their own superhuman abilities.

As the series progresses, Sathanas continues to influence Senator Hilltop, who becomes Vice President and then President, and attempts to manipulate the Next Men for his own ends. As part of this effort, he brainwashes Jasmine into believing that she is his wife and that her time with the Next Men was merely an involved dream. Towards the end of the series, Hilltop has sex with Jasmine and develops powers similar to Sathanas, leading him to realize that Sathanas is in fact a future version of himself in an example of a predestination paradox.

In issue #7, a backup story, "M4" (Mark IV) started. It dealt with an android, Mark IV, or "Mark Ivey" as one character called him. Initially appearing as a separate storyline, eventually the series started to tie into the Next Men storyline, and finally merged with it in issue #23.

Second series (IDW, 2010–2011)

The 2011 miniseries (which Byrne labels with a "3" in superscript beside each issue number, to continue the numbering of the original series) expands on the time-travel and alternate-reality plots from the initial series, picking up from the cliffhanger ending by stranding each teammate and Agent Murcheson in divergent time periods. Nathan ends up stranded in Nazi Germany and is experimented on by a Nazi scientist. Jasmine is stranded in Elizabethan era England, and succumbs to the Plague. Murcheson is stranded in the South during the American Civil War and is forced into slavery; she later escapes and uses her knowledge of the past to prevent the assassination of Abraham Lincoln. Bethany is stranded in a futuristic setting by an unknown captor, who claims to be punishing her friends for having betrayed her.

It is later revealed that Bethany's captor is Bethany herself, who came from a future alternate timeline where an accident left her buried alive for over 200 years and drove her insane. Having been retrieved by scientists who mastered control over time, she ended up travelling to the past and kidnapped her former friends to scatter them throughout time. Soon, the scientists who retrieved Bethany arrive to stop her. They then retrieve Jasmine and Nathan, and one of the scientists, Gil, reveals to them his intention to send them back in time one last time to prevent Sathanas from arriving in 1955 (thereby undoing the events of the original Next Men series).

Jasmine, who has second thoughts about the mission, backs out, leaving Nathan and Bethany to go alone. Having successfully arrived in 1955, Bethany explodes a bomb which prevents the arrival of Sathanas and his mutates.

A sequel series, titled Next Men: Aftermath, by Byrne was published by IDW after the conclusion of the Next Men series proper. The sequel continued the numbering from the original series, starting with #40 and concluding with #44.^[9]