"Pretty Guardian Sailor Moon Crystal: Season III" adapts the "Death Busters" arc from the original manga, focusing on the Sailor Guardians' battle against a new threat. The story begins with Usagi Tsukino, the titular Sailor Moon, and her friends encountering mysterious disturbances caused by the Death Busters, a sinister organization seeking to harness the power of the legendary Holy Grail to summon the entity known as Pharaoh 90. The Death Busters target innocent individuals, implanting them with parasitic creatures called Daimons to extract their pure hearts, which are necessary for their plans.

The narrative introduces two new Sailor Guardians: Sailor Uranus (Haruka Tenoh) and Sailor Neptune (Michiru Kaioh), who operate independently from Usagi and her team. Their aloof and secretive nature creates tension, as they prioritize the greater good over individual lives, often clashing with Sailor Moon's compassionate approach. Sailor Saturn (Hotaru Tomoe), a mysterious and powerful figure, is also introduced, with her true identity and role in the conflict gradually revealed. Hotaru, a frail and enigmatic girl, becomes central to the story as her connection to the Death Busters and her potential to awaken as Sailor Saturn are explored.

The Death Busters are led by the enigmatic Professor Tomoe, who conducts unethical experiments to further their goals. His daughter, Hotaru, is revealed to be a vessel for Mistress 9, a malevolent entity working with Pharaoh 90. As the story progresses, the Sailor Guardians uncover the truth about the Holy Grail and its connection to Sailor Moon's ultimate transformation into Super Sailor Moon. The climax involves a high-stakes battle against Mistress 9 and Pharaoh 90, with the fate of the world hanging in the balance. The resolution sees the Sailor Guardians uniting their powers to defeat the threat, while Hotaru's true destiny as Sailor Saturn is fulfilled, leading to a bittersweet yet hopeful conclusion.

The season maintains a focus on themes of sacrifice, unity, and the balance between destruction and rebirth, staying true to the manga's darker and more mature tone compared to earlier adaptations. The characters' relationships, particularly the dynamic between Usagi, Haruka, and Michiru, are explored in depth, adding emotional weight to the narrative. The story also delves into the lore of the Sailor Guardians, expanding on their roles as protectors of the solar system and their connection to the Silver Millennium.