The story begins with the marriage of Ingrid Kurtz to Lt. Friedrich Werner Weidt of the 1--th Regiment of the Wehrmacht in 1938. Unfortunately for the young bride, her handsome new husband turns out to also be a Complete Monster with ties to Nazi superscience, who volunteers their unborn child for genetic experimentation that will make the baby suitable to one day help produce, along with one of the other experimented-on children, the final planned generation of "supermen".

And thus, Adrian Weidt is born in 1939.

The story of Ingrid's hellish marriage, the young Adrian's eerily advanced intelligence showing up before he's even two years old, and the death of Ingrid's second child Klara is intercut with the goings-on at an Italian medical start-up called Gene Co, where Giuseppe Largo and his son Rottissimo, or Rotti, are doing some medical experimentation of their own, though at this point with a far more benign purpose. When the Weidts flee to America and become the Veidts, the scope expands again to encompass the American rash of superheroes, the equally unpleasant childhood of young Walter Joseph Kovacs, and the rise of Dr. Manhattan. Ingrid and Adrian end up each contributing to the murder of Friedrich Weidt, but Ingrid herself dies only a few months later, leaving Adrian to seek his fortunes elsewhere.

By the 1960s, Gene Co is in America as well and now run by Rotti Largo, there is a deadly outbreak of organ failures, and Veidt and Kovacs have both taken on costumed identities as crimefighters, alongside others such as the brutal Comedian, hopeful Nite Owl and the young Silk Spectre, who in many ways becomes the glue of the heroes' shaky partnership. Veidt is reunited with a childhood acquaintance named Anna, and they briefly fall in love before an acrimonious breakup. At around the same time, a young schoolgirl named Lucie Baillon is raped by a young pimp, is thrown on the streets by her parents, and ultimately gives birth to a child she names Adrien, who becomes the great joy of her life. Anna meets another man, Michael, while still pregnant, who promises to help raise her children, but he turns out to be working for a government conspiracy related to the same program that produced Adrian and Anna themselves, but he chooses to help her dodge the program anyway. He ends up shot for his trouble, and while Anna is trapped by the agents of the breeding program her twin children are taken from her and denied names.

A young blind woman named Magdalene Defoe becomes a cabaret singer for money and is quickly introduced to the harsh realities of life in the lower echelons of the entertainment industry until she meets, and secretly falls in love with, Largo's fiancee Marni. Veidt enters into business and becomes acquainted with a Dr. Nathan Wallace, whom he brings along onto a partnership with Gene Co to cure the organ failures, but their experimental cures fail to save the Silk Spectre, who dies at seventeen. Wallace falls in love with Marni, who ends up leaving Largo for Wallace, and Largo murders her and frames Wallace for it, using his leverage in politics to make Wallace instrumental in his plan to legalize organ repossession. Veidt abandons their partnership in disgust and begins a slow plan to do something about this pending nuclear war business.

Anna's daughter undergoes severe brainwashing but represses it, while the girl's twin brother internalizes her memories and is warped into an Enfant Terrible. A chance encounter with Veidt leads to the boy's obsession with being Veidt's child, and the sociopathic child ends up eventually arranging events to get himself and his sister closer to the man after Veidt has retired from super-heroism. Veidt swallows his pride and asks Largo for help, but Largo refuses when he secretly discovers the twins are Veidt's children. The boy twin is left with a damaged skull and brain when he and his sister flee together, and Veidt begins to slowly kill Largo with poison.

The Keene Act is passed. Superheroes are outlawed in America. Kovacs, now fully consumed by his Rorschach persona, refuses to quit. Nite Owl/Dan Dreiberg quits and remains friends with the increasingly isolated Veidt.