Tatsumi is a fighter who, accompanied by his two childhood friends, sets off to the Capital in search of a way to make money to assist his poverty-stricken village. After being separated from his friends, Tatsumi not only fails to enlist in the army, but is swindled out of all his money. He is then taken in by a noble family who offer him help, but intend to torture and kill him, just like they did with his friends and dozens of other people. Tatsumi is rescued by a group of assassins known as Night Raid, and is invited to join their ranks. Composed of the swordswoman Akame, a young woman armed with a huge pair of scissors named Sheele, the string manipulator Lubbock, the armored warrior Bulat, the sniper Mine, the beast fighter Leone and their leader Najenda, a former general of the imperial army, Night Raid is also part of the revolutionary forces assembled to overthrow Prime Minister Honest, who manipulates the infant emperor for his and his men's personal gain, leading the rest of the nation to poverty and strife.

Each member of Night Raid carries one of the "Imperial Arms" (帝具 Teigu?), items created via alchemy and parts of the supernatural Danger Beasts over 900 years ago. Forty-eight of these items were created and about half of them have been lost to history. These items range from weapons like swords and firearms to more utilitarian items including a cosmetic box and armor, and even organic beings such as a shape-shifting dog and a powerful warrior. The Imperial Arms cannot be used by just anyone, as their users must be compatible with them or risk death. The power of most Imperial Arms is so overwhelming that it is said that when two Imperial Arm users fight each other, one is bound to die. Tatsumi and his new friends successfully assassinate some of Honest's most trusted cohorts, while losing Scheele and Bulat to the enemy forces, with Tatsumi inheriting Bulat's Imperial Arm. This leads the Prime Minister to enlist the help of General Esdeath, considered to be the most powerful fighter in the Empire, who assembles her own team of Imperial Arms-wielding assassins, the "Jaegars", to hunt down Night Raid, who gains two new members, the Human-like Imperial Arm Susanoo and the master of disguise Chelsea.

After Night Raid defeats most of the Jaegars while losing Chelsea and Susanoo and the revolution gains momentum, Honest forms a new secret police force, the "Wild Hunt", led by his own son, Syura. However, the Wild Hunt heavily abuses its authority by killing innocent civilians for fun, making enemies of both the Jaegars and Night Raid. After a confrontation between Wild Hunt and the Jaegers, with casualties from both sides, Esdeath is able to blackmail Honest into disbanding the rest of Wild Hunt while Syura is killed by Lubbock after he captures both him and Tatsumi. Lubbock is killed while attempting to escape, and Tatsumi is sentenced to a public execution, but the remaining members of Night Raid attack the execution site to rescue him.
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