Chapter 1 opens in 1981 with June Morrissey in Williston, North Dakota, an oil boom town, after she has left Gordie Kashpaw and her son yet again. She dies trying to walk home in a snow storm. Part two of chapter one is in the first person voice of Albertine Johnson, June's niece, who receives a letter from her mother informing her that her Aunt June is dead and buried. Her mother did not invite her to the funeral, and as a result, Albertine refuses to speak to her. Two months after receiving the letter, Albertine goes home to the reservation. Albertine tells stories about June: her mother dying, father running away, marrying her cousin, leaving Gordie and King Kashpaw, returning only to leave again. During Albertine's visit to the main house (where all Kashpaws were welcome), the entire family gathers. This opening chapter sets the tone for the subsequent altering of perspectives and going back through history.
In Chapters 2, 3, and 4 we become acquainted with Marie, Nector, and Lulu (the love triangle the novel is centered on) as young adults in and around the year 1934. We learn that Marie once wanted to be a nun and never really liked the Lazarre side of her family. Nector was always in love with Lulu but married Marie for reasons unbeknownst to him. We learn that Lulu always assumed she and Nector would be married, but when she found out about Marie, she went to Moses Pillager (Lulu's cousin and well-known medicine man) but left him, taking her first child (Gerry Nanapush) back home when Moses refused to move out from the wilderness.
In Chapters 5, 6, 7, and 8 Erdrich explores the complexities of parenthood and infidelity for Marie, Nector and Lulu. We are acquainted with Lulu's 9 children and Marie's 7 children. Chapter 5 occurs in 1948; chapters 6, 7, and 8 occur in 1957. Chapter five deals with June being adopted by Marie, and later raised by Eli. Part two of chapter 5 is about the controlling power and rage of Marie's mother-in-law, Rushes Bear. Marie gradually warms up to Rushes Bear. In chapter 6 we learn about the death of Lulu's first (legal) husband, Henry Lamartine and Lulu's affair with his brother, Beverly Lamartine, during Henry's funeral. Years later, Beverly decides to go home to the reservation and claim his son, Henry Jr. Instead, Beverly is seduced by Lulu, forgets about claiming his son, and returns to the city. Chapter 7 is the turning point in the novel, because this is where the love triangle (Marie, Lulu and Nector) gets demolished. Nector and Lulu begin an affair that will last five years and produce a son, Lyman Lamartine. Then, Nector decides to leave Marie and marry Lulu. He leaves a note for Marie (which she later ignores completely), and takes a letter to Lulu. But while Nector waits for Lulu he accidentally burns down her home. When Lulu runs in to save her son, she burns all her hair off and it never grows back.
Chapters 9 and 10 focus on the brothers Henry Lamartine Jr. and Lyman Lamartine in 1973 and 1974. Chapter 9 recounts Albertine Johnson running away from home as a 15-year-old. She meets Henry Lamartine Jr., and loses her virginity to him. Chapter 10 is about Henry Jr. and Lyman and the car they bought together. Lyman recounts the many road trips before Henry Jr. went off to war, before he returned a very changed man. Their first road trip afterward turns out to be tragic: Henry Jr. jumps into the river, toward his death, and try as he might, Lyman could neither find nor save him.
Chapters 11 through 18 occur between the years 1980 and 1985, when Nector enters his "second childhood" and Marie and Lulu become friends in the retirement community.
Chapter 11 shows Albertine working with Gerry Nanapush's girlfriend at a weigh station. We learn that Gerry Nanapush is a prisoner and frequent escapee.
Chapter 12 focuses on Gordie's alcoholism following June's death. He has nearly drunk himself to death when one night he thinks he sees June's ghost. He goes to the car not thinking about how drunk he is and subsequently runs into a deer. He decides to put the deer in the backseat but forgets this and hallucinates that he has in fact killed June. He panics and goes to the convent where he drunkenly confesses to a nun. The police are called and Gordie runs away.
Chapter 13, entitled "Love Medicine (1982)" is central to the book. We learn that the entire family of Kashpaws/Pillagers/Nanapushes had/have special gifts of healing and insight. Lipsha Morrissey says, "I got the touch." As we learn from Lyman later in the novel, the Pillagers were members of the Midewiwin (medicine men and women who were blessed by the Higher Power to help others.
Nector has entered his "second childhood" and is unbearable for Marie because all he refers to is Lulu who is living in the retirement community with Marie and Nector. Lipsha is relatively young, 18 or 19 years old when his adopted grandmother, Marie, asks him to work love medicine on Nector. Love medicine, as Lipsha explains it, should always be used with extreme caution. Lipsha and Marie plot how to get Nector to eat a male goose heart while Marie eats a female goose heart. Lipsha chooses geese because they mate for life, and Marie wants him to be faithful. Nector refuses it and taunts Marie by putting the heart in his mouth but not swallowing. Marie is furious and smacks Nector on the back to make him swallow, but instead Nector chokes to death. Naturally, Lipsha and Marie are grieved, but by the end of the chapter Marie says, "Lipsha... you was always my favorite."
Chapter 14 shows of Marie nursing Gordie through his sickness (alcoholism).
Chapter 15 is Lulu's 1st person perspective. Lulu tells the story of her house burning down, and subsequently, the ending of her affair with Nector. The day Nector dies, Lulu is in recovery from surgery (possibly the removal of cataracts). Because the facility is short on aides, Marie offers to take care of Lulu. This begins an unexpected and often difficult friendship between the two matriarchs of the extended family.
Chapter 16 (moved to the P.S. section in the 2009 edition) is told from Lyman's 1st person perspective. He is crushed by Henry Jr.’s death and takes a year to mourn him. Eventually, Lyman ends up in Indian politics and policy. Ironically, he is re-assigned by the BIA to set up the factory his father (Nector Kashpaw) had begun years earlier.
After a workers riot, Lyman closes the factory and, by chapter 17 (entire chapter deleted from the 2009 edition), has a grand idea for the building: bingo, and later, a sex house. He has made up his mind.
In chapter 18, Lipsha is back at the retirement community when Lulu demands that he speak with her. She tells him about his parentage (which everyone on the reservation knows except Lipsha). She tells him because she has little to lose: "I either gain a grandson or lose a young man who didn’t like me in the first place." Lipsha goes to visit King (his half-brother) to learn more about Gerry, who escapes prison that very night and meets Lipsha: "So many things in the world have happened before. But it’s like they never did. Every new thing that happens to a person, it’s a first. To be a son to a father was like that. In that night I felt expansion, as if the world was branching out in shoots and growing faster than the eye could see." Lipsha drives Gerry to Canada.