In the world of Prester, flight is the dominant mode of transportation, made possible by Claudia Fluid: a liquidized form of the crystals that are produced on the planet. An organization known solely as the Guild has absolute authority over the skies, with a monopoly on the engines that make use of this fluid. Moreover, as ecological disasters destabilize the warring countries of Anatoray and Disith, the Guild also arbitrates in the disputes between the two. Caught in the middle of the conflict are Sky Couriers, piloting small, two-person vanships that fly freely through the sky. Last Exile follows the adventures of two teenagers who dream of surpassing their parents: Claus Valca, son of a famous vanship pilot, and Lavie Head, Claus' best friend and navigator. Their job as couriers entails passing through an air current called the Grand Stream that separates the hostile nations, which even standard airships struggle to survive. However, when they take on a high-rated delivery to bring an orphan girl named Alvis Hamilton to the battleship Silvana, they get dragged into a much greater conflict that pits them against the might of the Guild.

Jubei Kibagami wanders feudal Japan as an itinerant swordsman-for-hire. After a past betrayal left him masterless, he has no more patience for warring political factions and their schemes. Unfortunately, both past and political intrigue collide when he meets and saves a female ninja named Kagero from a man with the ability to make his body as hard as stone. The sole survivor of a ninja clan, Kagero continues her team's last mission: investigate a mysterious plague that wiped out an entire village. Jubei wants nothing to do with this, but the stone-like man's allies, a group of ninja with supernatural powers known as the Devils of Kimon, make that option difficult. To make matters worse, a government spy poisons Jubei, promising him an antidote if he can unravel the true intentions of the Devils of Kimon and their connection to the plague. The trail leads to shadow leaders, a plot to overthrow the government, and a man that Jubei thought he would never see again.

Kurumi is a beautiful young woman whose beloved boyfriend, Hal, died in a sudden airplane accident. Left heartbroken and gloomy, she isolates herself in a small house. But this soon comes to change when her grandfather requests the help of a humanoid robot named Q01. Taking on the appearance of Hal, Q01 is sent to Kurumi's house in order to save her from her state of despair. As Hal returns day after day and increases his efforts, Kurumi, despite her initial reluctance, slowly begins to open up to him and break free from her depression. But there is more to Hal than meets the eye, and these two will soon learn an unexpected truth about this relationship between a human and an android.

In a magical world where humans, demihumans, and oni are heavily at odds with each other, a princess named Saltorine Sally Aldike is on a journey to find a person named Mikoto Kibitsu. Traversing the world, Sally comes across many truths that she had been ignorant of due to her lineage—including the knowledge that the oni possess power potent enough to wipe out humanity. Seemingly blessed with a way to counter the oni's might, Sally has a strange power that manifests itself as a sigil resembling a peach, giving her superhuman abilities capable of defeating powerful oni with ease. Even so, Sally refuses to discriminate between humans, demihumans, and oni as much as possible, believing that peace between the three factions could be attainable one day. On the contrary, Mikoto—who also has the same ability as Sally's but with greater mastery—has a different goal. Mikoto is out to kill and torment all oni in existence, stopping at nothing to fulfill this objective. As Sally and Mikoto continue to cross paths, the power they possess will spell the difference between amicable coexistence and utter annihilation.