The story takes place in the Taishō era Japan, where a secret organization, known as the Demon Slayer Corps, has waged a longtime war against demons for centuries. These demons are former humans who possess supernatural abilities such as super strength, rapid regeneration, and unique powers referred to as "Blood Demon Art." Demons can only be killed if they are decapitated with weapons crafted from a rare alloy called Nichirin, injected with a poison extracted from wisteria flowers, or exposed to direct sunlight.

In contrast, the Demon Slayers are entirely human but employ specialized elemental breathing techniques known as "Breathing Styles." These techniques grant them superhuman strength and increased resilience, enabling them to fight demons effectively. The most formidable Demon Slayers hold the title of "Hashira", and gain this rank, through killing a member of the Twelve Kizuki, a group comprising the twelve strongest demons of their kind, or killing fifty demons through multiple advancements in their rank.