Nanapush is an elder of the Chippewa tribe, around fifty years old at the story's start. Having lost his wives and children to disease, he takes on the responsibility of guiding the survivors and preserving the tribe's traditional stories. He is deeply skeptical of the white government's treaties and land allotments, relying instead on his knowledge of old medicine and survival skills to protect his chosen family.

Pauline is a young, mixed-blood girl who feels isolated and invisible to others. Desiring to leave the reservation and live as a white woman, she moves to the town of Argus for work. She possesses a highly imaginative and insecure nature, developing a complicated jealousy toward Fleur Pillager's physical presence and unapologetic connection to the tribe's traditions.

Fleur is the sole survivor of the Pillager clan, a family known for their wild ways and deep connection to the natural world. Physically strong and fiercely independent, she lives alone at Matchimanito Lake. The surrounding community views her with awe and terror, whispering that she controls the lake monster and wields dangerous traditional medicine.

Margaret is the formidable, sharp-tongued matriarch of the Kashpaw family. Blindly loyal to her kin, she attempts to control her sons' choices to ensure her own security in her old age. She is physically tough and unapologetic in her opinions, balancing her practice of Catholicism with a practical understanding of tribal survival.

Eli is a young, capable hunter who feels a powerful attraction to Fleur Pillager. Despite his mother's strenuous objections and the terrifying rumors surrounding Fleur, he is determined to win her affection. He looks to the older generation, specifically Nanapush, for guidance on how to navigate the traditional methods of courting and survival.

Lulu is the brash, intelligent, and spirited daughter of Fleur Pillager. She serves as the silent audience for Nanapush's storytelling. Raised in the shadow of her mother's formidable reputation and the ongoing struggles over tribal land, she inherits much of Fleur's fiery energy.

Father Damien is the young, dedicated Catholic priest assigned to the reservation. While he represents the encroaching white religion, he genuinely cares for the Chippewa people and frequently advocates for them during crises. He attempts to bridge the gap between Catholic doctrine and the harsh realities of reservation life.

Moses is Fleur's cousin and one of the few surviving members of the Pillager clan. The trauma of the epidemic has driven him to live in total isolation on an island. He retains a deep knowledge of traditional medicine and is widely feared by the community, who seek him out only when desperate for potent remedies.

Bernadette is a wealthy widow who maintains a disciplined, highly organized farm on the northern part of the reservation. She is skilled in nursing the sick and preparing the dead for burial. As a prominent member of the Morrissey clan, she adapts to the changing economic conditions with an eye toward preserving her family's property.

Napoleon is Bernadette's older brother, a man who struggles with alcohol and lives on the fringes of his sister's successful farm. He represents the decline of some tribal members as they succumb to despair. He becomes an object of Pauline's misguided curiosity.

Pete is the owner of the Argus butcher shop where both Fleur and Pauline find employment. He runs a male-dominated environment where his hired men frequently play cards and drink. He is a businessman who tolerates the rough nature of his employees.

Lily is one of the men employed at the Argus butcher shop. He is intensely threatened by Fleur's physical strength and her consistent ability to beat him at evening card games. His wounded pride and suspicion of her skills fester into deep hostility.

Dutch is a white man married to Pauline's Aunt Regina, working alongside Lily and Tom at Pete Kozka's shop. He participates in the men's nightly card games and shares their collective humiliation as Fleur steadily wins their wages.

Tom is the third member of the butchering crew at Pete Kozka's shop. Like Lily and Dutch, he grows increasingly angry and suspicious of Fleur's card-playing prowess, allowing his frustration to override any sense of decency.

Nector is Margaret Kashpaw's younger son, a bright nine-year-old boy who embraces the changing world more readily than his brother Eli. He shows a keen interest in how land allotments and government fees work, adapting his survival instincts to the new systems imposed by the white authorities.

Clarence is Bernadette Morrissey's adult son. He aligns himself heavily with the rival Lazarre clan in the bitter disputes over reservation land sales. He is driven by greed and old family resentments, willing to use physical force against vulnerable elders to force his clan's agenda.

Boy Lazarre is a member of the Lazarre clan, a family eager to take the logging companies' money and push others to do the same. He is a physically imposing young man who holds deep-seated grudges against the Kashpaw and Pillager families.

Sophie is Bernadette's teenage daughter, a young girl whose naivety makes her vulnerable to the manipulations of others. She becomes a pawn in Pauline's complex web of jealousy and vengeance, leading to severe disruptions in the broader community.

Russell is Pauline's younger cousin, living in the town of Argus. He spends his time around the butcher shop, observing the adults' actions with a quiet detachment that mirrors Pauline's own disconnected nature.

Fritzie is Pete Kozka's wife, a woman who helps run the butcher shop business. Her departure for a summer vacation inadvertently leaves the volatile butchering crew unsupervised during a critical time.

Regina is Pauline's aunt who is married to a white man, Dutch James. She lives in Argus and represents the mixed-blood existence that Pauline initially strives to emulate, though she proves incapable of handling Pauline's increasingly peculiar behavior.

Edgar is an officer for the tribal police. Tasked with managing the aftermath of the consumption epidemic, he is utterly terrified of the Pillager family's reputation and refuses to help Nanapush rescue Fleur from her contaminated cabin.

The son of the original tribal police officer, Edgar Junior steps in to fulfill the duties his father was too terrified to complete. He reluctantly helps Nanapush handle the grim task of burying the epidemic's victims on Pillager land.

Philomena is one of Bernadette Morrissey's teenage daughters. She resides on the bustling farm, observing the daily routines of nursing and agriculture that her mother expertly manages.

Izear is an older man with six children from a previous marriage. He enters the community's narrative as a prospective husband for Sophie Morrissey, carrying dark rumors about his past that trouble the rest of the reservation.