Kyoto has been populated by groups of tanuki and tengu for years, living alongside humans who are oblivious to the existence of these creatures. Yasaburou Shimogamo is the third son of an influential tanuki family who spends his carefree days taking care of an old tengu, observing humans through his ability to shapeshift, and dealing with the mysterious woman named Benten. Behind the peace and tranquility, however, is a painful memory from long ago as Yasaburou's father, head of the tanuki community, was killed and eaten by a group of humans known as the Friday Fellows. Uchouten Kazoku follows the trials and tribulations of the Shimogamo brothers as they struggle to avoid their own grisly demise while coming ever closer to unraveling the truth behind their father's death.

In a dystopian future where Japan's political organization has crumbled after the Great Tokyo War, Japan is broken up into 10 independent nations, with each nation controlled by a gang led by a "Best," a human-proclaimed prophet with destructive superpowers. Nozomi Moritomo is a "Rest"—a normal girl that has just started out as a rookie in the local gang. She wants to help the Best Masami Utoku, her childhood friend and role model, in the ongoing territorial dispute. When Masami becomes severely injured and unable to fight, Nozomi decides to go on a mission to complete the requests sent to Masami from all over Japan. Along the way, she meets Yukina Kosaka, a shy girl with no sense of direction; Ai Hibiki, an upbeat girl who loves eating; and Chiaya Misono, a quiet and mysterious girl that wears a gas mask. Together, the four girls travel all over the country on their motorcycles while getting involved in territorial wars, disagreements, and even suspicious conspiracies.