Maka is a scythe meister, working to perfect one particular scythe until it is good enough to become Death's Weapon -- the weapon used by Shinigami-sama, the spirit of Death himself. As if that wasn't unusual enough, her scythe is a demon scythe called Soul Eater, which can change form from a scythe to a human-looking boy.
In order to make Soul Eater powerful enough to be Death's Weapon, he must eat the souls of 99 humans and 1 witch.
Along the way, the two of them face many different challenges, including a cat witch named Blair (who happens to have a thing for Soul) and a teacher who's been turned into a zombie (and wants him to join her!). Her fellow students, like the shadow ninja weapon meister named Black Star who always needs to be the center of attention, aren't much help, either.
It'll be a miracle if Maka even survives, let alone manages to make Soul Eater into the Death Scythe.