"Sekai-ichi Hatsukoi" is a romantic anime series centered around the lives of individuals working in the publishing industry, particularly in the manga and literary departments. The narrative primarily revolves around Ritsu Onodera, a talented editor who leaves his father's publishing company to prove his capabilities independently. He joins Marukawa Publishing's shojo manga department, where he is assigned to work under Masamune Takano, a strict and demanding editor-in-chief. Unbeknownst to Ritsu, Takano is actually his first love from high school, whom he had forgotten due to a misunderstanding that led to their separation.

The series explores the rekindling of their relationship as Ritsu and Takano navigate their professional and personal lives. Ritsu struggles with his feelings for Takano, often denying his emotions due to pride and past heartbreak, while Takano remains determined to win Ritsu back. Their dynamic is marked by tension, humor, and gradual emotional growth as they confront unresolved issues from their past.

In addition to the central romance, the series features several side stories involving other characters in the publishing world. These include the relationship between Yoshiyuki Hatori, a senior editor, and Chiaki Yoshino, a manga artist who hides his profession from his family. Another subplot follows Shouta Kisa, a reserved editor, and Yukina Kou, a popular novelist with a playful and flirtatious personality. Each storyline delves into the challenges of balancing personal relationships with professional responsibilities, as well as the complexities of love and communication.

The anime is structured into episodic arcs that focus on different characters, providing a broader perspective on the interconnected lives within the publishing industry. Themes of self-discovery, forgiveness, and the pursuit of happiness are woven throughout the narrative, creating a multifaceted portrayal of romance and ambition. The series combines lighthearted moments with emotional depth, offering a balanced exploration of its characters' journeys.