The story is set in the future on the planet named Amoi which is controlled by a supercomputer named Jupiter. Among the mostly male human population, the light-haired elite class is allowed to temporarily keep the dark-haired mongrels as pets. One elite member, Iason, encounters a mongrel named Riki in the slums and decides to take him in. However, Iason keeps Riki longer than it is socially approved, and rumors abound about their possible relationship.

Centuries ago, Kanna, a princess and the last of a winged race, was held prisoner in a castle as she was feared by the rest of the world. However, when she met a soldier named Ryuuya, she fell in love with him and told him of her wishes to see the outside world and to find her mother. Ryuuya attempted to fulfill these wishes. However, his efforts were in vain as Kanna was sealed in the sky through magic and cursed to be in pain for all eternity. Hundreds of years later, Yukito, a decendant of Ryuuya, comes to a quiet town one week before their annual festival with hopes that he can make some money. However, when he meets an unusual girl called Misuzu, he is reminded of what his mother once told him—When you go out on your journey, if you find the winged girl's re-incarnation, you must use your power to set her free. Yukito and Misuzu's fates soon become intertwined with each other, with each developing feelings for the other. However when Yukito realizes Misuzu's connection to the past, he must decide on whether to leave, or to attempt to break the curse that has bound Kanna in centuries of pain.

After escaping certain death, Kei Nagai and his new companion Kou Nakano plot revenge on Satou, their fellow Ajin who is hellbent on world domination. As Satou embarks on a string of public executions, the human race rushes to come up with a solution to stop the immortal villain. Kei discovers unlikely allies in the form of two former adversaries: high-ranking government official Yuu Tosaki, whose extensive research on Ajin gives him a tactical advantage in the fight against Satou, and Tosaki's Ajin assistant Izumi Shimomura. As his faction continues to gather allies, Kei races against time to put a stop to Satou's crusade before it brings about an end to civilization as he knows it.

Although her name means snow white, Shirayuki is a cheerful, red-haired girl living in the country of Tanbarun who works diligently as an apothecary at her herbal shop. Her life changes drastically when she is noticed by the silly prince of Tanbarun, Prince Raji, who then tries to force her to become his concubine. Unwilling to give up her freedom, Shirayuki cuts her long red hair and escapes into the forest, where she is rescued from Raji by Zen Wistalia, the second prince of a neighboring country, and his two aides. Hoping to repay her debt to the trio someday, Shirayuki sets her sights on pursuing a career as the court herbalist in Zen's country, Clarines. Akagami no Shirayuki-hime depicts Shirayuki's journey toward a new life at the royal palace of Clarines, as well as Zen's endeavor to become a prince worthy of his title. As loyal friendships are forged and deadly enemies formed, Shirayuki and Zen slowly learn to support each other as they walk their own paths.