Salamanca Tree Hiddle is a thirteen-year-old girl who has moved to Euclid, Ohio from her beloved hometown of Bybanks, Kentucky after her mother, Chanhassen Pickford Hiddle, left home for a cross-country bus tour and never came back. After learning that Chanhassen isn't coming home from Idaho, Sal's father John Hiddle decides to move Sal and himself to Euclid, a suburb of Cleveland and a far cry from the pastoral atmosphere and wide-open spaces Sal knows and loves. John moves to Euclid because he knows a woman there named Margaret Cadaver who helps set him up with a job. Margaret and John met shortly after they learned Chanhassen wouldn't be returning, and they kept in contact via phone and writing each other letters. Sal wants absolutely nothing to do with Margaret, and despite her dad's frequent attempts to explain the nature of his relationship with Margaret, Sal refuses to hear him out. She acclimates to school in Euclid well enough and makes friends with her classmate and neighbor, Phoebe Winterbottom, who's going through her own domestic drama. As Sal's mother's birthday approaches, Sal's grandparents, Gram and Gramps Hiddle, take her on a road trip across the country to visit her mom in Idaho. Sal approaches the trip with a sense of urgency, because she believes that if there will ever be an opportunity to bring her mom home, it will be on her birthday.
Sal's grandmother asks her to tell them a story as they drive. Sal decides to tell them about Phoebe, her over-dramatic best friend whose mother suddenly vanishes one day. Shortly after Sal and John move to Euclid, Phoebe invites Sal to her house for dinner after being impressed by Sal's bravery when she catches a spider and removes it from the classroom. By coincidence, Phoebe lives next door to Margaret Cadaver. Phoebe suspects that Margaret is a lunatic who murdered her husband. Phoebe's family is polite, "respectable," and obsessed with cholesterol. Mr. Winterbottom is a cartographer and Mrs. Winterbottom is a homemaker, but Sal suspects that Mrs. Winterbottom's sunny disposition is a mask she wears to hide her dissatisfaction in her domestic role.
One Saturday, Sal is at Phoebe's house when the doorbell rings and the girls see a young man of about eighteen standing outside. They answer the door and he asks if it is the Winterbottom home. Phoebe asks if he would like to leave her mother a message but he declines. Phoebe is convinced he will return and ambush them so they head out to visit their friend Mary Lou Finney. The Finneys' home environment is the opposite of Phoebe's; everyone is wild, happy, and spontaneous. Sal is immediately drawn to Mary Lou's cousin, Ben, who lives with Mary Lou's family.
Phoebe's mother decides that they should not mention the young man at the door to Phoebe's father. Phoebe finds an anonymous note at the door that says "Don't judge a man until you've walked two moons in his moccasins." The arrival of the note spooks everyone and nobody seems to know why it might have been left or for whom.
Sal's Gram is starting to feel sorry for Mrs. Winterbottom but nonetheless presses Sal to continue. By now, the Hiddle road trip has reached Madison, Wisconsin. They eat at Ella's Kosher Deli and Ice Cream Parlor, followed by lemon tea and blueberry muffins at the Steep and Brew. They then visit the Wisconsin Dells where they tour an old fort and watch Native American performers dance and play drums in a circle. In school, Sal has always been told to call Indians "Native Americans," but her mother is a descendant of the Seneca people, and she always hated the term "Native Americans" and thought American Indian was a stronger, more noble label.
Leaving Madison, they head through the lower rim of Minnesota where Gram wants to hear more about Phoebe. Sal resumes the tale and reveals that Phoebe received more messages; each message has some kind of moral or concise life lesson, as one might find on a fortune cookie. Phoebe's conviction that all strangers are potential axe-murderers starts to rub off on Sal. While they are buying candy at the drugstore, Sal feels someone watching them; she looks around and sees the young man who visited Phoebe's house looking for Norma. Ben walks the girls home and Phoebe shows her mother the second note.
Gram and Gramps are caught up in the story and as they detour through Pipestone they discuss what the cryptic sayings might mean. They visit Pipestone National Monument and smoke peace pipes and stay overnight at Injun Joe's Peace Palace Motel. The next day Sal tells Gram and Gramps about Mr. Birkway. Sal suspects he is not all there, because he is too excitable for a teacher. He has given a summer assignment to the class to keep a journal; everyone is horrified when he wants to read them aloud. Sal was not at the school when the assignment was given so he allows her to just write one or two sample entries instead. One Saturday, Sal and Phoebe notice him in Margaret Cadaver's backyard where he and Mrs. Cadaver dig around a rhododendron tree; Phoebe suspects that that is where Margaret buried her husband's body. Neither girl thinks Sal's father should visit her anymore.
In Sioux Falls, the weather is scorching, so Gramps pulls off the highway and he and Gram wade in the lake. Sal joins them. Her hair floats all around her in the water and it reminds her of her mother's hair. They see a boy on the shore going through Gramps's pants pocket. Sal is frightened of him but before she can react Gram flails in the water and realizes she has been bitten by a poisonous snake, a water moccasin. Gramps swims her back to the riverbank and the boy lends Gramps his knife so that he can make a slit in Gram's leg to let out the snake venom. The boy sucks out the wound and accompanies them to the hospital where Gramps insists on lying in the hospital bed with her. She is a difficult patient and insists on being released from the hospital the next day. They continue driving towards the Badlands and Sal resumes her story.
Phoebe arrives home from school to find a note from her mother telling her to keep all the doors and windows locked and to call her father if she needs anything. This doesn't sound that worrisome until Phoebe's sister Prudence opens her note which asks her to boil spaghetti and heat up the sauce. Their father's note said she had to leave for a few days but offers no explanation. Phoebe believes her mom has been kidnapped and wants to call the police but her father observes a lunatic kidnapper would not have allowed her to label the food in the freezer for them and write notes. Phoebe tells her school friends that her mother is on a trip to London. At home she searches for clues, finding supposedly strange spots on the carpet that she marks with tape, and collecting some unknown hair strands in an envelope. Feeling sorry for Phoebe, Sal invites her to spend the weekend at her house. Phoebe accepts but is a difficult and demanding guest. She hopes her mother will have returned by Monday but she has not. She has apparently called Margaret Cadaver to let her know all is well but Phoebe finds this very suspicious and thinks Mrs. Cadaver has murdered her mother and has made up the story about the telephone call to hide this.
Eventually, Phoebe goes to the police herself, Sal in tow. The police do not take their suspicions seriously and call Phoebe's father to pick the girls up from the station. Phoebe is upset because nobody takes her fears seriously. Sal begins to prepare Phoebe for the reality that her mother might have left for good, but Phoebe won't let her talk this way. On their second visit to Sergeant Bickle, Sal notices that the "lunatic" young man who keeps showing up at Phoebe's house is in a couple of the photographs on the police officer's desk. It appears he is the sergeant's son.
Back on Sal's street, she runs into Mr. Birkway who is picking up Mrs. Partridge to take her somewhere. In the course of a short exchange, Sal discovers that he is Margaret Cadaver's twin brother. Sal tries to tell Phoebe that Mr. Birkway is Margaret's twin before he reads her journal aloud to the class, but Phoebe won't let her speak. Mr. Birkway is surprised to discover what Phoebe has written about his sister in her journal, and after reading it, he stops reading people's journals out loud. Mr. Birkway visits Phoebe at home and tells her that although Margaret's husband is dead, she did not murder him. He was killed by a drunk driver and their mother was blinded in the accident. Margaret was a nurse who was on call in the emergency room when they were brought in. Phoebe feels very guilty for getting her scenario so wrong but is still baffled as to her mother's whereabouts. When Sal tells her the lunatic is Sergeant Bickle's son, they devise a plan to track him down.
Sal breaks off her story when she and her grandparents arrive at Old Faithful, a natural geyser that still bubbles and erupts. It is an incredible sight and brings Gram to tears as she has always wanted to see it in person. As they whiz through Montana, Sal resumes the story. Sal calls every Bickle in the telephone book until she reaches the right house, and when she finally connects to Sergeant Bickle, she asks to speak to his son. The sergeant gives her his address at school and Sal and Phoebe visit the university campus on Saturday. At the bus stop they run into Ben who is going to visit someone in the hospital. At Chanting Falls university they head to Mike Bickle's dormitory and after claiming to be his cousins are directed to his door. On the way, Sal spots Mike Bickle, a.k.a. the lunatic, sitting on a bench holding hands with Phoebe's mother. Phoebe watches them, angrily, but Sal cannot watch and runs as far as possible the opposite way. Finding herself at the hospital she asks to see Mrs. Finney but cannot go up to her ward as she is not family. She is directed to the garden where she sees Ben sitting with a woman wearing a pink robe. It is his mother and Sal is reminded of her own mother who was in a similar mental state after losing her baby. The attraction between Sal and Ben reaches a climax and they finally kiss each other. Returning to the university, Sal finds Phoebe at the bus stop. Phoebe is furious that her mother has cut her hair and changed the way she does her make-up. When they get home, Prudence tells them that their mother called and she is coming home. Phoebe makes Sal come over for support.
Mrs. Winterbottom is glad to see her husband but has brought Mike with her to introduce him to the family. She admits that she had never told her husband for fear of what he might think of her, but Mike is her son, and she gave him up for adoption before she even met her husband. Sal leaves, realizing this is a situation she should not be involved in. Phoebe leaves with her and as they go they find Mrs. Partridge placing a cryptic note on the step.
Gram interrupts the story by announcing they are in Idaho. They press on to Coeur d'Alene to stay the night before the final leg to Lewiston, where Sal's mother is. Gram is tired but wants to hear what happened to Phoebe. She also wants to know why Mrs. Partridge had been leaving notes on the Winterbottoms' porch. This was something Sal and Phoebe also wanted to know, so they ask her. She actually viewed them as nice surprises, not as potentially ominous and frightening, and she chose them from the sayings that Margaret read out of the newspaper.
When Sal returns home from the Winterbottoms' the night Norma brings Mike home, Ben is sitting on her front step. He has brought her a chicken and named it Blackberry.
Gram is disappointed that the story has ended. She seems to be getting weaker, so when they get to Coeur d'Alene they go directly to the hospital where they learn she has had a stroke. She is unconscious but Gramps insists on staying with her because they have been side by side for fifty-one years. Sal feels guilty and thinks the snake bite triggered the stroke. Gramps gives her the car keys and some money, knowing that she still wants to go to Lewiston. Sal can already drive, having learned on their farm. She drives slowly but determinedly and in four hours arrives at the top of Lewiston Hill. Halfway down she finds an overlook where a man points out the one thing she is looking for: the top of the bus that skidded off the road eighteen months ago in an accident that left only one person alive. Sal crawls down to the bus, wanting to look for anything familiar. When she returns to the car there is another car parked behind hers; when the sheriff hears her story he drives her to Longwood, to the Snake River, so that she can visit her mother's grave. She hears birdsong and knows that the tree is singing.
The sheriff drives her back to Coeur d'Alene and they talk about the bus accident. He doesn't know if he saw her mother, but he remembers seeing Mrs. Cadaver, who had been sitting in the seat next to Sal's mother and was the only survivor of the crash. It was not until Sal sees the bus and the gravesite that she truly believes her mother has died.
Back at the hospital, her grandfather has left a note letting them know he is at the motel and that Gram passed away. Sal and Gramps stay in Coeur d'Alene to make all the arrangements to have Gram's body flown back to Bybanks and buried in the aspen grove where she and Gramps were wed. After Grams' death, Sal and her father move back to Bybanks, back on their farm with Sal's grandfather living with them. Ben and Phoebe write to her all the time and are planning a visit. After finally coming to terms with her mother's passing, Sal is able to begin the process of grieving and healing.
