At the elite Ninja Academy, first-grade students known as Nintama, a playful contraction of ninja and egg, begin their training. Among them is the lively and bespectacled Rantaro, a boy from a low-ranking ninja family whose parents hope he will one day become a master ninja. He is joined by his two closest friends: Shinbei, the wealthy son of a merchant, and Kirimaru, who lost his father in a war. Together, these three underdogs form a tight trio, and despite their poor grades and tendency to prioritize food and fun over their studies, they navigate the daily chaos of a school where faculty members can materialize in flashes of light and classroom pranks often involve lethal projectiles.

The school itself is a vibrant, almost cartoonishly exaggerated world where the classes are color-coded, with Rantaro and his first-year classmates wearing bright blue uniforms while older students wear more muted tones. The peace of the academy is disrupted when assassins from the Usetake ninja clan target Yukitaka Saito and his son Takamura. Yukitaka now runs a popular barbershop, but he and his son are former members of the Usetake clan, and their past has caught up with them. Rantaro and his friends decide to protect the father and son, launching them into a complicated adventure that pits them against hired killers with grotesque, caricatured features.

As the plot unfolds, the trio finds themselves in an arduous race against time that culminates in a desperate climb to ring a bell at a mountaintop Buddhist temple. The boys must use their unconventional skills and unwavering team spirit to overcome the assassins and save their new friends. The adventure showcases their amazing feats of ninja derring-do, which are often immediately followed by very down-to-earth pratfalls. Through booby traps, slapstick battles, and the guidance of their gruff headmaster and his sympathetic younger colleague, the young Nintamas ultimately prove that even the most mischievous and unlikely students can become heroes, returning to their academy to continue their unconventional education.