"Lycoris Recoil: Friends are thieves of time" centers on a covert organization known as DA (Direct Attack), which operates under the Japanese government to maintain public safety. The organization employs young girls called Lycoris, trained as elite assassins, to eliminate threats discreetly. The story primarily follows Chisato Nishikigi, a cheerful and highly skilled Lycoris with a unique moral code, and Takina Inoue, a disciplined and serious operative reassigned to Chisato's team after a mission goes awry. The two form an unlikely partnership, balancing their contrasting personalities and approaches to their work.

The narrative unfolds as Chisato and Takina take on various missions, ranging from neutralizing criminals to uncovering larger conspiracies threatening national security. Their dynamic evolves from initial friction to mutual respect and camaraderie, with Chisato's optimism and Takina's pragmatism complementing each other. The series delves into the moral complexities of their roles, exploring themes of justice, loyalty, and the cost of maintaining peace through covert operations.

A central plotline involves the emergence of a mysterious hacker group targeting DA, exposing vulnerabilities within the organization and raising questions about its true motives. As Chisato and Takina investigate, they uncover secrets about DA's operations and its connection to a shadowy figure from Chisato's past. This discovery forces them to confront their own beliefs and the ethical implications of their actions.

The series balances action-packed sequences with moments of character development, highlighting the personal struggles and growth of its protagonists. Supporting characters, such as Mika, Chisato's mentor, and Kurumi, a tech-savvy ally, contribute to the narrative by providing additional layers of intrigue and assistance in their missions. The interplay between the characters and the evolving stakes of their missions drive the story forward, culminating in a climactic confrontation that tests their resolve and bonds.