"Azur Lane" is set in an alternate world where humanity faces a mysterious alien threat known as the Sirens. To combat this danger, nations form alliances and develop advanced warships with humanoid forms called "Kansen" or "shipgirls." These shipgirls are anthropomorphized versions of historical warships, each embodying the characteristics and abilities of their respective vessels. The story primarily revolves around the conflict between two major factions: the Azur Lane alliance, comprising shipgirls from the Eagle Union (United States), Royal Navy (United Kingdom), and Sakura Empire (Japan), and the Red Axis, led by the Iron Blood (Germany) and Crimson Axis (Italy).

The narrative begins with the Azur Lane alliance achieving a significant victory against the Sirens, but internal tensions arise as the Iron Blood and Sakura Empire defect to form the Red Axis, seeking to harness Siren technology for their own purposes. This schism leads to a fractured world where former allies become adversaries. The protagonist, a young and inexperienced Commander, is assigned to the Azur Lane base and tasked with leading a diverse group of shipgirls in the ongoing war against both the Sirens and the Red Axis.

Key characters include Enterprise, a stoic and powerful aircraft carrier from the Eagle Union; Belfast, a loyal and efficient maid cruiser from the Royal Navy; and Akagi, a cunning and ambitious aircraft carrier from the Sakura Empire who becomes a central antagonist. The Commander's journey involves navigating complex alliances, managing the personalities and abilities of the shipgirls, and uncovering the true nature of the Sirens. As the story progresses, it delves into themes of loyalty, sacrifice, and the consequences of wielding advanced technology.

The plot intertwines historical naval warfare elements with science fiction, exploring the moral dilemmas of using Siren technology and the blurred lines between friend and foe. The series balances action-packed naval battles with character-driven moments, highlighting the relationships and rivalries among the shipgirls. The overarching mystery of the Sirens' origins and motives adds a layer of intrigue, driving the narrative toward a climactic confrontation that challenges the survival of humanity and the future of the shipgirls.