Jeannette Walls is riding in a taxi in contemporary New York City, on her way to an event, when she looks out the window and sees her mother digging through trash. Although Mom has been homeless for years, Jeannette feels a sudden sense of shame and gloom about Mom's life and begins to reflect on her childhood and how Mom and Dad's choices affected her.
The Walls opens the door to her childhood, beginning when Jeannette is three-year-old and standing on a chair to reach the stovetop as she boils her own hotdog. Her pink dress catches on fire, and she gets horribly burned. After a few days in the hospital, Dad shows up, lifts Jeannette out of bed and they do "the skedaddle," leaving the hospital without paying the bill.
Much of Walls' memories of her childhood in the desert focus on "the skedaddle" and how the Walls family — Mom, Dad, Lori, Jeannette, Brian, and, eventually, little Maureen — move to different desert towns, settling in for as long as Dad can hold a job. However, Dad's paranoia about the state and organized society, coupled with his alcoholism, leads them to move frequently. They settle down in a small mining town, Battle Mountain, Nevada, for a few months and Jeannette and Brian spend countless hours exploring the desert. Mom even takes a break from her art projects to hold down a job as a teacher to extend their stay. A minor altercation with law enforcement, however, compels the family to pick up and move to Phoenix where Mom has inherited a house from her mother.
At first, Phoenix offers the family some stability; Mom's house is large and has a yard and the children enroll in school. Dad is able to keep a steady line of electrician jobs going for awhile. However, once again, his alcoholism gets the best of him. Jeannette is so bothered by it that she asks him to give up drinking for her tenth birthday. He goes sober for a few weeks, but then, after their car breaks down in the desert and the family has to accept the charity of a stranger for a ride back to Phoenix, Dad runs back to the drink to drown his sense of shame. Mom, in need of more adventure, suggests they move to Welch, West Virginia, where Dad grew up. She thinks maybe his family can help them out. Dad is reluctant, but eventually piles into the family's latest lemon of a car and they head east.
Welch turns out to be more depressing than any of them wants to admit. First, Dad's mom is an abusive woman who takes sexual advantage of Brian — suggesting that she also abused Dad when he was younger. The town is impoverished, segregated, and does not welcome newcomers. The family stays put, however, and Mom and Dad buy a shack on the top of a hill for the family to live in. The structure is decrepit; it has no indoor plumping or central heating and has a leaking roof. Dad's drinking gets worse and the kids are often hungry. As Jeannette enters adolescence she contemplates more and more her parents' choices and rails against them for being irresponsible parents. She and her older sister Lori hatch an escape plan: Lori will move to New York City when she graduates and Jeannette will follow her there. And, despite some setbacks, the girls accomplish this dream.
In New York City, Jeannette is surprised how quickly she is able to find a job and get work as a reporter, which is her goal in life. She and Lori eat well and love having a roof over their head, warm water, and heat. They eventually ask Brian and Maureen to move in with them. The kids enjoy their new lives together; however, Mom and Dad feel abandoned and move to New York City. Neither Mom nor Dad is able or willing to keep a steady job, and they end up becoming squatters in an abandoned building. While Lori, Jeannette, and Brian are able to secure jobs and build new lives, Maureen is unable to care for herself and, in a bout of insanity, stabs Mom. Maureen ends up in a mental institution. The family drifts apart. Dad, with a lifetime of chain-smoking and drinking, is dying although he is barely sixty years old. When he dies of a heart attack, Jeannette is forced to examine her own life and realize that while she has pushed away her parents and her past, part of her thrives on the reckless freedom they instilled in her. She divorces her husband, moves, and eventually finds peace with her past and her present.