Issue 1 starts with a crowd watching the televised funeral service of J’onn J’onnz, the Martian Manhunter. At the same time in a tower block apartment, is the man partially responsible for J’onn’s death, Dr Light who is confronted by Crispus Allen, The Spectre. Held accountable for J’onn’s death, Light is transformed by the Spectre into a candle that burns until the Spectre snuffs him out.
Sister Clarice, a nun, dies in a hospital.
Avenging J’onn’s death, the Spectre finds and kills Effigy, setting him aflame and imprisoning him in a Green Lantern power battery.
The Question, Renee Montoya, is pursued by members of the Order of the Stone whom she was supposed to lead. Defeating them, the Question manages to get aboard a ship sailed by other members of the Order that sails out to sea.
The Spectre confronts the actual killer of J’onn J’onnz: Libra. He is, however, unable to harm him and instead kills the villains known as the Hangmen with whom Libra was dealing.
Off the coast of England, the Order of the Stone manages to raise the Spear of Destiny and, as the Question attempts to stop them, they end up stabbing her with it.
Crispus Allen attempts to give up the role of the Spectre but is instead sent to the boat that the Question is on and, as the Question is shown to have survived the attack from the Spear of Destiny, the Spectre appears and pronounces her judgment is at hand.
Issue 2 sees the Question recognise the Spectre as her old Gotham City partner Cris Allen. Despite his personal feelings, the Spectre must carry out his judgment upon the Question but offers a last kindness, transporting them both off the ship but, deliberately or otherwise, leaving the Spear of Destiny on board and in the hands of the Order of the Stone.
The Spectre takes the Question back to Gotham and briefly explains that he was indeed Cris Allen before showing her a vision of Batwoman, the Question’s old lover from earlier times, fighting against Killer Croc. With this she realises that he does indeed mean to kill her. On the rooftop of Gotham PD, despite protesting that she had become head of the Order of the Stone to fight them from within, the Spectre attacks her but is stopped at the last minute by the Radiant, the embodiment of God’s Mercy as the Spectre is God’s Vengeance. The Spectre rejects the Radiant and her host, the nun Clarice who died in the first issue, refusing to accept God has mercy following the Spectre’s killing of his own son soon after Cris Allen joined with the spirit of Vengeance. In tears, Allen breaks down before the Radiant.
Elsewhere, the Order of the Stone have transported the Spear of Destiny to one of Vandal Savage’s hideaways. Savage confronts them and willingly accepts being stabbed by the Spear and is revealed to be not just an immortal caveman but Cain himself, the first murderer, whose mark is emblazoned on his face. He demands to know the location of the one who marked him: the Spectre.
Sister Clarice counsels Cris Allen over the death of his son and attempts to convince him that his work as the Spectre is just and should continue despite his reluctance. They are interrupted by the arrival of Captain Maggie Sawyer and others, all of whom have fallen to the influence of the Anti-Life Equation, unleashed at the end of Final Crisis #3. Before they can infect the Question, the Radiant teleports her away to safety where she finds Batwoman lying bloodied and seemingly unconscious. Attempting to help her, Batwoman instead grabs her throat as she, too, has succumbed to the Anti-Life Equation.
Issue 3 begins with the world’s population infected with Anti-Life. The citizens of Gotham congregate outside a church where the Spectre and the Radiant are attempting to hold them off.
Nearby, Batwoman brutally beats the Question, breaking her arm as she tries to make her submit to Anti-Life. She is stopped – and the Question rescued – by the arrival of the Spectre and the Radiant. The Spectre cages Batwoman and intends to kill her before the Question begs him to stop. As the crowd of Gothamites approach, the Radiant transports them away.
Vandal Savage, still bearing the mark of God and the Spear of Destiny, marshals his followers and leads them towards Gotham.
Seeking sanctuary, the Radiant, Spectre and Question hide within the church where the Radiant heals the Question of her wounds. Within moments, other survivors join them and the church is quickly surrounded by a horde of Gothamites under the influence of Anti-Life. The Question and the Radiant realise the crowd are waiting for Cain – Savage – to arrive and fulfill the prophecy in the Crime Bible. As they wait with the other survivors, the Radiant notices three men who huddle for safety and identifies them as the men who killed her human host, Sister Clarice. She wonders why the Spectre, as God’s Vengeance, is not called upon to judge them.
Savage arrives and calls upon the Spectre to face him. Despite the Question’s protests, the Spectre goes out and confronts him but is beaten and stabbed with the Spear of Destiny.
Issue 4 begins with Vandal Savage torturing the Spectre and his human host, Cris Allen. Using the Spear of Destiny, he manages to sever the link between the two beings, chaining the Spectre to himself and enslaving him while the Question and the Radiant look on, helpless. As Savage turns to the Question, the Radiant tries to stop him but, at Savage’s command, the Spectre forces her away. Savage attempts to kill the Question for her betrayal and refusal to serve in his order but she is somehow protected from the power of the Spear. As he attempts to wound her with it, the Question is rescued by the Huntress and before Savage can react, the Radiant sets up a barrier around the church, allowing the Question and Huntress to escape inside, along with the corpse of Cris Allen.
Inside, the Question begins to ponder about why the Spear did not harm her and though she tries questioning the Radiant, the latter will not provide answers. She states that it is humanity that must make the choices. However, she does give the Question and Huntress a history of the Spear and they realise that the Question may be able to use it against Savage. First, though, they must retrieve it.
Realising that if they were to rejoin the Spectre with its host, Allen, they might have a chance once more, the Radiant confronts Savage but before she can do anything, Savage has the Spectre speak the Anti-Life Equation. He speaks it so loudly that across the globe, people fall under its spell and even the Radiant begins to despair.
Issue 5 starts with the entire world having succumbed to the the Anti-Life Equation and the spirit of Cris Allen wondering whether Vandal Savage is right when he says God is dead. The Radiant starts to lose hope and her protection of the church begins to weaken, forcing the Question and the Huntress to decide they need to get the Spear away from Savage sooner rather than later.
Together they confront Savage, the people and former heroes of Gotham attacking them, as the Spectre pleads with Allen to help him. As he ponders, the Question and Huntress are overpowered and Savage stabs the Question with the Spear which, with the help of the survivors in the church, leads to the Question getting hold of the weapon herself. The Radiant, however, gives her a choice of using the Spear to help Allen and the Spectre or herself; she chooses the former and, whole once more, the Spectre purges the world of the Anti-Life Equation as the Radiant heals the Question.
Those who joined willingly with Savage are killed by the Spectre, their leader restrained. The Spectre banishes Savage to Africa, his identity as Cain revealed to all who seem him, leaving him with no peace nor safety ever again.
Despite the Huntress asking, the Question does not reveal how she helped Allen achieve peace, though we see that his son, whom he had to kill when he first became the Spectre to avenge the murder the boy committed, had been returned to life.