After the Battle of Sekigahara, a samurai is tasked by the Ieyasu shogunate to raise a band of assassins to finish off Toyotomi's allies and other ambitious warlords, to prevent another civil war.
Azumi, played by Aya Ueto, is discovered as a 7-8 year old girl weeping next to the body of her dead mother by the samurai master Gessai, played by Yoshio Harada, and his entourage of young students. Azumi is raised in the martial skills of samurai and shinobi sword fighting, and the art of assassination. Azumi and her fellow classmates, now at young adult age, are constantly being told about a "mission" they must accomplish, though they have no idea what this mission is yet.
Prior to setting out on their mission, their master orders his students to "pair up" with each others' best friend and proceed to kill each other, thus out of 10 students only five will remain to proceed with the mission. Questions and internal conflicts begin to arise amongst Azumi and her comrades as it seems their mission even prevents them from saving a village of mostly women and children from being masacred at the hands of a group of bandits, as their primary mission is to kill the warlords Asano Nagamasa, Masayuki Sanada and Kiyomasa Kato. Aside from the warlords, Azumi must also deal with a narcissistic mercenary, "swordsman in white", whose sword has no handguards as he claims to never have had to defend against attacks.