In a dystopian future where humanity has declined, robots dominate the world, but they are plagued by the "Ruin," a mysterious phenomenon causing their bodies to decay. Casshern, a once-legendary warrior, awakens with no memory of his past. He is haunted by fragmented recollections of his role in the death of Luna, a figure revered as the "Goddess of Moonlight," whose demise triggered the Ruin. As Casshern wanders the desolate landscape, he is relentlessly pursued by robots who believe consuming his immortal body will grant them salvation from decay.

Throughout his journey, Casshern encounters various characters, each grappling with the inevitability of death and the meaning of existence. Lyuze, a vengeful robot, seeks to kill Casshern for his role in Luna's death but gradually develops a complex relationship with him. Ohji, a kind-hearted robot, and his companion Ringo, a young girl who views the world with innocence, provide moments of warmth and humanity amidst the bleakness. Friender, a robotic dog, becomes Casshern's loyal companion, aiding him in battles against relentless foes.

The narrative explores themes of mortality, guilt, and redemption as Casshern struggles to reconcile his past actions with his present identity. Flashbacks reveal his origins as a weapon created by the scientist Dr. Azuma, who sought to create eternal life. Casshern's existence is intertwined with Luna, whose death he inadvertently caused, leading to the Ruin. As he confronts his past, Casshern grapples with the question of whether he deserves to live or if his existence perpetuates suffering.

The series is structured episodically, with each episode introducing new characters and their struggles against the Ruin. These encounters often culminate in philosophical dialogues about life, death, and the nature of existence. The overarching plot builds toward a confrontation with Braiking Boss, the ruler of the robot world, who seeks to harness Casshern's immortality to reverse the Ruin. The climax reveals the cyclical nature of life and death, with Casshern ultimately choosing to embrace his role in the world's renewal rather than its destruction.

Casshern Sins is a contemplative and atmospheric series, blending action with existential inquiry. Its narrative is driven by the protagonist's internal conflict and the broader implications of his existence in a decaying world. The characters' interactions and the unfolding mystery of the Ruin create a poignant exploration of humanity, even in a world dominated by machines.