"Uncle From Another World" centers on Yousuke Shibazaki, a man who awakens from a 17-year coma to reveal that his consciousness was transported to a fantasy world during that time. In this other world, Yousuke, now referred to as "Ojisan" (Uncle), lived as an adventurer, honing his skills in magic and combat while navigating a realm filled with monsters, magic, and political intrigue. Upon returning to modern-day Japan, he struggles to adapt to the mundane realities of his old life, often comparing it to his extraordinary experiences in the fantasy world.

The narrative alternates between Yousuke's present-day life and flashbacks to his adventures in the other world. In the present, Yousuke lives with his nephew, Takafumi Takaoka, who becomes his primary connection to modern society. Takafumi helps his uncle navigate contemporary technology and social norms, often serving as a bridge between Yousuke's fantastical past and his mundane present. Yousuke's eccentric behavior, shaped by his time in the other world, frequently leads to humorous and awkward situations, particularly as he attempts to integrate into a society that has moved on without him.

The flashbacks to the other world reveal Yousuke's growth from an inexperienced outsider to a powerful and respected figure. His journey is marked by encounters with unique characters, including elves, demons, and other adventurers, as well as his mastery of unconventional magic. These memories are often triggered by events in the present, creating a parallel narrative that enriches the story's depth. The contrast between the two worlds highlights Yousuke's internal conflict as he grapples with nostalgia for his fantastical past and the challenges of reintegrating into a world that feels alien to him.

Key characters include Takafumi, who provides a grounded perspective on Yousuke's eccentricities, and Mabel, an elf from the other world who shares a complicated history with Yousuke. Mabel's occasional appearances in the present day add layers to the story, as her interactions with Yousuke reveal unresolved tensions and unspoken emotions from their shared past. The series balances humor, action, and emotional depth, exploring themes of identity, belonging, and the impact of extraordinary experiences on ordinary lives. The interplay between Yousuke's dual realities drives the narrative, offering a unique blend of fantasy and slice-of-life storytelling.