"Teasing Master Takagi-san" centers on the daily interactions between two middle school students, Nishikata and Takagi, who share a classroom and a unique dynamic. Nishikata is a well-meaning but easily flustered boy who often finds himself the target of Takagi's playful teasing. Takagi, a clever and observant girl, takes delight in outsmarting Nishikata, using her quick wit and perceptiveness to predict his reactions and turn situations to her advantage. The series unfolds through a series of lighthearted vignettes, primarily set in their school or neighborhood, showcasing their growing bond.

The narrative structure is episodic, with each episode featuring self-contained scenarios where Nishikata attempts to outwit Takagi or get back at her for her teasing. These attempts often backfire, as Takagi consistently stays one step ahead, leaving Nishikata embarrassed but secretly admiring her cleverness. Despite his frustration, Nishikata gradually begins to appreciate Takagi's company, and their relationship evolves into a subtle blend of friendship and mutual affection. The series avoids overt romantic declarations, instead focusing on the quiet, everyday moments that highlight their connection.

Supporting characters, such as their classmates Mina, Yukari, and Sanae, add variety to the story, often participating in or observing Nishikata and Takagi's interactions. These characters provide additional perspectives on the central duo's relationship, though the focus remains firmly on Nishikata and Takagi. The tone of the series is consistently warm and humorous, with a gentle pace that emphasizes the innocence and charm of adolescence.

Themes of youthful curiosity, the awkwardness of growing up, and the nuances of early relationships are explored through the lens of Nishikata and Takagi's interactions. The series captures the simplicity and sincerity of middle school life, portraying the small but meaningful moments that define their connection. While the plot is minimalistic, the strength of the series lies in its ability to convey emotion and character development through subtle gestures and dialogue, making it a relatable and endearing portrayal of young love and friendship.