"Sekai Ichi Hatsukoi - The World's Greatest First Love" is a romantic drama anime centered around the lives of individuals working in the publishing industry, particularly in the manga and literary departments. The story primarily revolves around Ritsu Onodera, a talented editor who leaves his father's publishing company to prove his capabilities independently. He joins Marukawa Publishing, where he is assigned to the shojo manga department, Emerald Editorial Division, under the supervision of Masamune Takano, his former high school classmate and first love.

Ritsu and Takano share a complicated past. During high school, they were in a romantic relationship, but it ended abruptly when Takano confessed his feelings, and Ritsu, overwhelmed and confused, rejected him. Years later, their reunion at Marukawa reignites unresolved emotions. Takano, who has harbored lingering feelings for Ritsu, is determined to win him back, while Ritsu struggles to reconcile his lingering affection with his pride and insecurities. Their dynamic is marked by tension, misunderstandings, and gradual rekindling of their bond.

The series also explores the relationships of other characters within the workplace. Yuu Yanase, a manga artist, and Chiaki Yoshino, an editor, share a tumultuous relationship rooted in their professional collaboration and personal history. Their story delves into themes of trust, jealousy, and the challenges of balancing work and romance. Additionally, the series introduces Shouta Kisa, a reserved editor, and Kou Yukina, a cheerful and outgoing manga artist, whose relationship evolves from a professional partnership to a deeper emotional connection.

The narrative intertwines the personal and professional lives of its characters, highlighting the pressures of the publishing industry while exploring themes of love, self-discovery, and second chances. The workplace setting provides a backdrop for both comedic and dramatic moments, as the characters navigate deadlines, creative differences, and their evolving relationships. The series balances lighthearted humor with emotional depth, offering a multifaceted portrayal of romance and personal growth.