"Appleseed XIII" is a 13-episode anime series set in a futuristic world where humanity has rebuilt society after a global war. The story takes place in Olympus, a utopian city governed by a supercomputer called Gaia and inhabited by humans, cyborgs known as Bioroids, and genetically engineered soldiers called Clones. The narrative centers on Deunan Knute, a skilled soldier, and her partner Briareos Hecatonchires, a cyborg, who serve as members of ESWAT, an elite counter-terrorism unit tasked with maintaining peace in Olympus.

The series explores the fragile coexistence between humans and Bioroids, who were created to stabilize society but face discrimination and resentment from some human factions. Deunan and Briareos are drawn into a series of conflicts involving rogue elements within Olympus, including terrorist groups and corrupt officials who seek to disrupt the city's harmony. Their missions often involve uncovering conspiracies, thwarting attacks, and confronting enemies who exploit the tensions between humans and Bioroids.

Key characters include Hitomi, a Bioroid and the administrator of Olympus, who plays a pivotal role in maintaining the city's balance. Her decisions and actions are frequently scrutinized, as she navigates the ethical dilemmas of governing a society with diverse populations. Another significant figure is Yoshitsune, a mysterious and skilled warrior with ties to Deunan's past, whose motives and allegiances remain ambiguous throughout the series.

The plot delves into themes of identity, coexistence, and the ethical implications of artificial intelligence and genetic engineering. As Deunan and Briareos confront various adversaries, they also grapple with their own personal struggles, including Briareos' adaptation to his cyborg body and Deunan's loyalty to her ideals in a morally complex world. The series builds toward a climactic confrontation that tests the resilience of Olympus and its inhabitants, ultimately questioning the sustainability of a society built on technological and biological advancements.