"Kono Osu Buta!!" centers on the life of a high school student named Kenta, who unexpectedly finds himself in a bizarre situation after encountering a mysterious pig. This pig, named Osu, possesses the ability to speak and exhibits human-like intelligence. Osu claims to be a former human who was transformed into a pig due to a curse, and he seeks Kenta's help to break it. Reluctantly, Kenta agrees to assist Osu, setting off a series of comedic and chaotic events.

The narrative explores the dynamic between Kenta and Osu as they navigate the challenges of daily life while attempting to uncover the origins of the curse. Osu's presence disrupts Kenta's routine, often leading to humorous misunderstandings and awkward situations, particularly at school and in social interactions. Despite Osu's brash and self-centered personality, a bond begins to form between the two, with Kenta gradually becoming more invested in helping Osu regain his human form.

Supporting characters include Kenta's classmates and family members, who are drawn into the chaos caused by Osu's antics. These characters often serve as foils to the central duo, adding depth to the story through their reactions and interactions. The plot occasionally delves into more serious themes, such as the nature of identity and the consequences of one's actions, but the tone remains predominantly lighthearted and comedic.

As the story progresses, Kenta and Osu encounter various supernatural elements and individuals connected to the curse. These encounters provide clues about the curse's origins and the steps needed to break it. The series balances episodic humor with an overarching narrative, keeping the focus on the evolving relationship between Kenta and Osu while gradually unraveling the mystery behind Osu's transformation. The blend of comedy, fantasy, and slice-of-life elements creates a unique and engaging narrative that appeals to fans of light-hearted, character-driven stories.