"Zone of the Enders" is a science fiction anime series set in the 22nd century, where humanity has colonized Mars and its moons. The story revolves around the conflict between the Earth government, known as the United Nations Space Force (UNSF), and the Martian colonists, who seek independence. Central to the narrative is the Orbital Frame, a highly advanced humanoid mecha, which becomes a key weapon in the struggle for power.

The protagonist, Leo Stenbuck, is a young civilian living on the Martian colony of Antillia. During a UNSF attack on the colony, Leo accidentally pilots an Orbital Frame named Jehuty, a prototype machine with immense power. Jehuty is equipped with advanced AI and is capable of devastating combat abilities. Leo, initially reluctant and inexperienced, is thrust into the role of a pilot as he becomes a target for both the UNSF and Martian rebels. His journey is marked by personal growth, as he grapples with the moral complexities of war and the responsibility of wielding such destructive power.

The antagonist, Colonel Nohman, is a high-ranking UNSF officer who commands the Orbital Frame Anubis, a machine rivaling Jehuty in strength. Nohman's motivations are rooted in a desire for control and dominance, and he views Jehuty as a threat to his plans. The conflict between Leo and Nohman escalates as the series progresses, culminating in high-stakes battles that determine the fate of both Earth and Mars.

Supporting characters include ADA, Jehuty's AI, who assists Leo in combat and provides guidance, and Viola Gyunei, a Martian rebel who initially opposes Leo but later becomes an ally. The series explores themes of war, autonomy, and the ethical implications of advanced technology, as the characters navigate their roles in a larger political and military struggle.

The narrative is driven by intense mecha battles, strategic maneuvering, and the personal struggles of its characters. The series balances action with moments of introspection, as Leo confronts the consequences of his actions and the broader implications of the conflict. The story concludes with a decisive confrontation between Jehuty and Anubis, leaving the future of Mars and its inhabitants uncertain but hopeful.