In a world built around bread and baked goods, the kind-hearted baker Jam Ojisan works tirelessly in his bread factory, dreaming of creating living bread. After countless failed experiments, a miraculous star of life falls from the sky and strikes his oven, bringing to life the anpan he is baking. This creature, named Anpanman, is a superhero with a head made of anpan, a sweet bun filled with red bean paste. He dedicates himself to flying across the land on his red cape, searching for anyone who is hungry, lonely, or in trouble. His defining act of heroism is to tear off a piece of his own head and offer it to those in need, believing that the truest form of justice is to feed the starving, even if it weakens him.

The main setting is a cheerful, pastoral world centered around Jam Ojisan's bread factory, where a large cast of food-based and animal-based characters live. Anpanman's closest allies include the quick-tempered but brave Currypanman, whose head is a curry bread, and the elegant and gentle Shokupanman, whose head is a square loaf of bread. They are supported by Batako, Jam Ojisan's flustered but loyal assistant, and Cheese, a dog who became Anpanman's devoted friend after being saved from starvation. The primary antagonist is Baikinman, a self-proclaimed genius inventor from Baikin Star who resembles a germ or bacterium. He constantly schemes to destroy Anpanman and spread filth and mischief, piloting various mecha from his secret base. He is joined by Dokin-chan, a spoiled and selfish girl who has a hopeless crush on Shokupanman and often acts against her own brother's plans out of jealousy or whim.

Anpanman has a significant weakness: his strength drains when his head is damaged, soiled, or wet. Whenever he returns to the bread factory in a weakened state, Jam Ojisan bakes him a fresh new head, revitalizing him to continue his battles. This cycle of sacrifice and renewal is central to the narrative. The story arcs expand as more characters are introduced: Melonpanna, a sweet and gentle friend; her sister Rollpanna, who struggles with a dual personality; and many others drawn from Japanese cuisine, animals, and fairy-tale motifs. The conflicts are typically episodic: Baikinman launches a plot to take over the town or corrupt the land, and Anpanman and his friends rally to stop him, often overcoming their own personal flaws or fears in the process. Underlying every adventure is a consistent philosophy drawn from the creator's wartime experiences: that real heroism is not about defeating an enemy with force, but about giving of yourself to alleviate the suffering of others.