Tanjiro is a teenage boy living in rural Taishō-era Japan who supports his family by selling charcoal after his father's death. He possesses an unnaturally keen sense of smell and wears distinctive hanafuda earrings. When his family is murdered, his intense sympathy and strong will drive him to join the Demon Slayer Corps in hopes of finding a cure for his sister.

Nezuko is Tanjiro's younger sister who transforms into a demon after surviving a brutal attack on her home. She retains her human emotions and protective instincts, fighting off her predatory urges to defend her brother. Instead of consuming humans for sustenance, she enters a deep, two-year hibernation state to replenish her energy.

Sakonji Urokodaki is an elderly veteran demon slayer who lives at the base of Mount Sagiri. He serves as a trainer for the Demon Slayer Corps and permanently hides his face behind a red tengu mask. Though his training methods are harsh and physically punishing, his severity stems from an intense desire to keep his students alive.

The Hand Demon is a massive, grotesque entity composed of thick, entangled arms. He harbors a deep, vindictive grudge against Urokodaki for imprisoning him on the wisteria-lined mountain nearly half a century ago. He specifically hunts recruits wearing fox-themed warding masks to inflict pain on his original captor.

Giyu is a fast-moving demon slayer armed with a katana. He operates under the strict belief that all demons are violent monsters who consume humans, until he witnesses Nezuko shield her vulnerable brother. Recognizing their unique bond, he sends the siblings to his former master rather than completing his execution orders.

Sabito is a young orphan who says he was taken in by Urokodaki. He appears wearing a protective fox mask adorned with a scar and wields a wooden sword. He spars aggressively with Tanjiro to force him to internalize his breathing lessons. He pushes the novice to his physical limits out of a desire to see Urokodaki's lineage succeed.

Makomo is an orphan girl who wears a floral robe and a partially exposed fox mask adorned with flowers. She acts as a patient teacher to Tanjiro. She corrects his form and explains the physiological mechanics behind total concentration breathing. Her calm instruction contrasts with Sabito's aggressive sparring methods.

Saburo is an elderly villager who lives near the Kamado family's mountain. He possesses a deep knowledge of local folklore and insists that dangerous creatures roam the woods after dark. His stern warning and offer of shelter inadvertently save Tanjiro from the massacre that claims the rest of his family.