The following version of this book was used to create the guide: Good, Michelle. Five Little Indians. HarperCollins Publishers Ltd, 2020.

Michelle Good's novel Five Little Indians is set in the 1960s and 1970s. The novel traces the lives of five Native characters who are interned at the residential Mission School as children. The novel is written from the first and third person points of view and employs the past and present tenses. For the sake of clarity, the following guide employs the present tense, and a linear mode of explanation.

When Maisie, Clara, Kenny, Lucy, and Howie are children, they are torn from their homes and families and taken to a residential school on an island. The Mission School is a Catholic institution run by Father Levesque. Brother John and Sister Mary are respectively in charge of the boys' and girls' dormitories and teach the children that their Native customs, traditions, and languages are shameful. Maisie, Clara, and Lucy cross paths while at the school, but do not develop relationships until later. Kenny and Howie grow close, because Howie becomes reliant upon Kenny for support and comfort. When Maisie and Clara turn 16, they leave the school, but Maisie tells Lucy to find her when she gets out. Meanwhile, Kenny helps Howie escape and later exacts his own liberation, too.

Kenny reunites with his mother, Bella, after fleeing the Mission. However, life at home proves unsustainable for Kenny, and he eventually takes a job on a boat. He develops a peripatetic lifestyle, moving constantly and taking odd jobs.

When Lucy turns 16, she gets out of the Mission and heads to Vancouver to find Maisie. Maisie lets her stay with her at her apartment and helps her get a housekeeping job at the hotel where she works. However, Maisie feels claustrophobic with Lucy around. She sneaks out at night and meets an old man whom she has aggressive sex with. She is forcing the old man to replicate the way that Father Levesque sexually abused her as a child. Not long later, Maisie starts to use heroin and eventually dies by suicide.

In the two years following Maisie's death, Lucy develops a friendship with Clara. She keeps working at the hotel until she gets her nurses license and starts her training program. Then one day, Kenny resurfaces and he and Lucy rekindle their childhood friendship. Shortly after they start sleeping together, Kenny disappears, leaving Lucy alone and pregnant. Clara and Lucy move in together and Lucy soon gives birth to a baby girl she names Kendra, after Kenny.

Kenny comes in and out of Lucy's life over the following years, but ultimately disappoints Lucy's hopes that he will be the husband and father that she and Kendra need. Clara assumes a significant role in the family's life given Kenny's absence. However, she soon feels stifled in this realm, too. She starts spending time at the Friendship Center, through which she meets and befriends George and Vera. They eventually lead her to their healer friend Mariah, who lives in the desert. While staying with Mariah one winter, Clara starts to heal from her childhood trauma.

After returning to Vancouver, Clara becomes a courtworker through the Native Courtworkers' Society. She is then assigned to Howie's case. Howie was also at the Mission School, and has been in trouble with the law for attacking Brother John and stealing a crucifix. Clara advocates for him and encourages him to value his freedom.

Some years later, former Mission School students sue the federal government for the abuses they suffered at the school. Lucy, Howie, Clara, and Kenny become involved in the case, hopeful that their testimonies will exact justice for them and their late friends. Not long later, Kenny dies. However, Lucy and Kendra maintain a life together, and Clara and Howie develop a romance and future.