In "LBX Girls," humanity faces an existential threat from the mysterious alien race known as the Colony. To combat this invasion, the United Nations establishes the Defense Artificial Intelligence Development Lab (DAIDL), which creates advanced humanoid weapons called LBX (Little Battler eXperience) Girls. These androids are designed to protect Earth by harnessing advanced combat capabilities and artificial intelligence. The story centers on a group of LBX Girls who awaken in a world on the brink of destruction, tasked with defending humanity while grappling with their own identities and purpose.

The protagonist, Prototype L, serves as the leader of the LBX Girls. Alongside her are other units, each with distinct personalities and combat specialties, such as the cheerful and energetic Prototype F, the calm and analytical Prototype S, and the reserved yet powerful Prototype P. As the LBX Girls are deployed to various battlefronts, they must confront not only the Colony's relentless forces but also the ethical dilemmas surrounding their existence as artificial beings. The narrative explores themes of identity, humanity, and the moral implications of creating sentient weapons.

The plot unfolds as the LBX Girls gradually uncover the truth about their origins and the motivations behind their creation. Tensions rise as they question whether they are mere tools or beings capable of forging their own destinies. The series balances intense mecha battles with introspective moments, delving into the emotional struggles of the LBX Girls as they form bonds with each other and the humans they are sworn to protect. The story builds toward a climactic confrontation with the Colony, where the LBX Girls must make critical decisions that will determine the fate of both humanity and themselves.