This guide was made with the following version of this book: DiCamillo, Kate. Louisiana's Way Home. Somerville: Candlewick Press, 2018.

Louisiana begins to write the journey of her life so that anyone who was ever curious could have an answer. Her story begins with the curse her great-grandfather put into motion generations ago, one that has haunted her family ever since, including her. Years later, her Granny rips her from her home in Florida in the middle of the night. Louisiana, usually used to her Granny's plans in the middle of the night, thinks nothing of it initially. However, she falls asleep and once she wakes, she realizes they are driving from Florida to Georgia. When Louisiana confronts her Granny, the older woman refuses to listen to her and Louisiana bemoans the loss of her friends Raymie Clarke and Beverly Tapinksi in Florida.

Once in Georgia, their car runs out of gas and they receive the assistance of a George LaTrell, who fills their gas for free. Vic, a gas station owner is kind to Louisiana as well, letting her take as many peanuts as she would like. Once back on the road, Louisiana has to take the wheel due to Granny becoming incapacitated from pain in her tooth. Never having driven before, Louisiana manages to get off the highway and finds a dentist in Richford, Georgia, who removes all the teeth from Granny's mouth.

They both manage to leave the dentist's office without paying the bill, but once in town, are forced to stay at a motel called Good Night, Sleep Tight. There, Louisiana meets the ornery Bernice, who refuses them a room without payment upfront. The room they stay in reminds Louisiana of her childhood before Florida, when her Granny took her around the country without ever settling. They settle in the room. Louisiana feels a little better after she meets a boy with a crow named Clarence on his shoulder, and who promises her free things from the vending machine in the motel.

The following morning, Granny is still recuperating and Louisiana is forced to sing for another night in the room. Bernice introduces Louisiana to the organ player at a church, Miss Lulu, and they are both impressed with her voice. While at the church, Louisiana wanders off and finds a phone in Reverend Frank Obertask's office. She tries to call her friends in Florida but does not know their numbers, nor is she able to navigate the operator system.

On returning to the motel, Louisiana runs into the boy with the crow. The boy's name is Burke Allen. Burke delivers on his promise and retrieves items from the vending machine. They talk about their lives, with Burke relating that he is the third generation of that name. Louisiana tells him about her curse, how in Elf Ear, Nebraska, her great-grandfather had sawed his wife in half and left her.

Burke takes Louisiana to his home and makes her bologna sandwiches, which she eats, also taking some with her. At the motel, she discovers her Granny is gone to Indiana to deal with the curse. Louisiana leaves a letter that relates how Louisiana was found in an alley and that they are not related. Upset, Louisiana lies to Bernice about her Granny being gone and runs to find Burke's home. She loses her way and falls in a hole, losing the letter. Louisiana is later discovered, still in the hole, by the Allen family. Once in their home, she meets the three Burke Allens and Betty Allen, the youngest Burke's mother.

Louisiana stays the night with the Allens, and in the morning decides to speak with Reverend Obertask, whom she hopes will provide her with answers. She finds him sleeping in his office and is accused of trying to steal his pipe by Miss Lulu. The Reverend awakens, dismisses Miss Lulu, and speaks gently to Louisiana. She asks him about her parents and why they would leave her, but he is unable to provide an answer, disappointing her.

Louisiana plans with Burke to leave for Florida but is stopped when Bernice refuses to release her luggage, promising to do so once Louisiana has sung at a funeral. Louisiana returns to the Allens and has dinner with them, crying from their kindness. The following day, Louisiana arrives at the funeral and raptures the crowd with her voice. While singing, she images seeing her Granny in the audience and is overwhelmed, fainting. She wakes in the Reverend's office, whom she tells her life story as he retrieves her luggage from the motel and drives her to the Allens. The Reverend encourages her to forgive her parents and her Granny, while the Allens offer to adopt her.

Torn, Louisiana is unable to come to a decision. While at the carnival with the Allens, she realizes the opportunity she has through the kindness they show her. After deciding to stay, the Reverend puts her in touch with her friends in Florida and they come to visit her. It is revealed that Louisiana has been writing down the events of the novel as a letter to her Granny. She ends her letter by telling Granny how things shook out with the Allens and that she has finally forgiven her.