Two years have passed following the Tendoshuu's invasion of the O-Edo Central Terminal. Since then, the Yorozuya have gone their separate ways. Foreseeing Utsuro's return, Gintoki Sakata begins surveying Earth's ley lines for traces of the other man's Altana. After an encounter with the remnants of the Tendoshuu—who continue to press on in search of immortality—Gintoki returns to Edo. Later, the regrouped Shinsengumi and Yorozuya begin an attack on the occupied Central Terminal. With the Altana harvested by the wreckage of the Tendoshuu's ship in danger of detonating, the Yorozuya and their allies fight their enemies while the safety of Edo—and the rest of the world—hangs in the balance. Fulfilling the wishes of their teacher, Shouyou Yoshida's former students unite and relive their pasts one final time in an attempt to save their futures.

Although the golden age of piracy is about to reach new heights, most people do not seek the glory of finding the elusive One Piece—a treasure signifying a new conqueror of all seas that was once embodied by the legendary King of the Pirates, Gol D. Roger. However, even if civilians generally despise pirates, they secretly cheer for at least one of them. One red-headed girl from Sabaody Archipelago is no exception: She reveres Nami, the ingenious female navigator of Monkey D. Luffy's Straw Hat crew. Determined to deliver a fan letter to her idol, the Sabaody child is prepared to challenge forces of authority who strive to prevent Luffy and his friends from departing for their next destination: the New World. But to succeed, Nami's fan may need to risk her life and interfere with the Marines' plans, potentially causing devastating consequences for the wider world.

Said to be humanity's natural enemy, formidable dragons that belong to an ancient bloodline roam the world. Only two ways prove effective to kill a dragon: freezing their blood with silverine—an aura that comes from silver weapons—or letting their bodies be incinerated by sunlight. Young hunter prodigy Leonica is accompanied by her close friend Ragna, who appears to lack the skills necessary in their profession. Moreover, many shun Ragna, considering him cursed because dragons always seem to attack him and slaughter his close ones. Nevertheless, Leonica sees potential in Ragna and gladly partners up with him. Likewise, Ragna feels certain that Leonica is immune to his misfortune thanks to her incredible strength. His confidence is shaken, however, when Ragna dreams of Leonica's death, believing this to be a prophecy. As the destined day arrives, he comes face-to-face with his future self, who bestows him enormous power and memories from the future to ensure Leonica's safety. In order to succeed, Ragna must join forces with a mysterious figure known as Crimson and eradicate all dragons for good.

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.