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 in a bandit attack, Tatsumi unsuccessfully attempts to enlist in the army and is swindled out of his money in the Capital. He is taken in by a noble family, but when an assassin group called Night Raid attacks, he learns that his noble hosts actually intended to torture and kill him as they had done to his friends.
As a result, he joins Night Raid, which consists of the swordswoman Akame, the beastly fighter Leone, the sniper girl Mine, the scissor-wielding Sheele, the string manipulator Lubbock, the armored warrior Bulat, and their leader Najenda, a former general of the imperial army. Night Raid is also part of the revolutionary forces assembled to overthrow the prime minister Honest who is manipulating the young emperor for his personal gain despite the rest of the nation falling to poverty and strife.
The members of Night Raid carry Teigu (帝具, anime: Imperial Arms), unique weaponry created 900 years ago out of extremely rare materials as well as legendary animals called Danger Beasts (危険種, kikenshu). The power of the Teigu is so overwhelming that it is said that when two Teigu users fight each other, at least one of them is bound to die.
Although Night Raid successfully assassinate some of Honest's cohorts, they lose Sheele during a fight against capital garrison member Seryu and then Bulat when Honest recruits the Empire's sadist general Esdeath and her Three Beasts. Tatsumi receives Bulat's Teigu, Incursio, as a result while Esdeath replaced her slain subordinates with a group of Teigu-using warriors called the Jaegers. Night Raid, along with new recruits Susanoo (a humanoid Teigu owned by Najenda) and Chelsea, fight the Jaegers with Seryu, Wave, and Akame's younger sister Kurome among its ranks. Over time, the two factions gradually lose some of their members.
When the revolution gains momentum, Honest forms a new secret police force, the Wild Hunt, led by his own son, Syura. But Wild Hunt heavily abuses its authority by killing innocent civilians for their own plans, antagonizing both the Jaegers and Night Raid. After a battle between Wild Hunt and the Jaegers, with casualties from both sides, Esdeath blackmails Honest into dissolving the rest of Wild Hunt. Syura is killed by Lubbock after he captures both him and Tatsumi. Lubbock is killed while attempting to escape, and Tatsumi is sentenced to death despite Esdeath's attempts to save his life. The remaining Night Raid members attack the execution site to rescue Tatsumi while being pursued by the imperial general Budo, who Mine manages to kill at the cost of her Teigu while falling into a coma.