Out of My Mind is told from the point of view of an eleven-year-old girl named Melody Brooks who was born with cerebral palsy. Melody cannot walk, talk, feed herself, or take herself to the bathroom. Her parents work hard at taking care of Melody. Their next-door neighbor, Mrs. Violet Valencia, also known as Mrs. V, is Melody’s part-time caregiver. Melody is extremely intelligent and absorbs all that she hears and sees. She has a photographic memory. She finds that she can hear colors and smell images when music is played. Melody wishes she wasn’t so restricted and wants to be able to live and communicate like any other kid.
When Melody is five years old, her mother takes her to a doctor, Dr. Hugely, to determine how smart she is and whether she can be enrolled in school. The doctor gives Melody inadequate assessments. He determines that Melody is severely brain-damaged. He suggests her parents send her to a school for the developmentally disabled or put her in a residential facility, so they do not have the burden of raising her. Her mother knows there is so much more to Melody and that she has true intelligence inside her. She tells Dr. Hugely he is wrong and insensitive, and she is going to enroll Melody in Spaulding Street Elementary School.
Melody starts elementary school and spends the next five years in a program designed for children with special needs. Initially, she is excited to be in classroom H-5, but eventually finds the learning program to be repetitive and unchallenging. When Melody was younger, her mother had attached a plastic tray to her wheelchair with common words, numbers, and phrases pasted on it for Melody to point to so she could communicate. Over time, that tray becomes too simplistic for Melody. Mrs. V wants to help Melody gain more language skills. She redesigns Melody’s communication board with a larger variety of nouns, verbs, adjectives, and pictures of people in her life so that Melody can point to them with her thumb and form a sentence. Mrs. V creates flash cards and teaches Melody new words every day. When Melody turns eight, her parents surprise her with a puppy named Butterscotch. A short time later, they welcome a new baby girl to the family, giving Melody a little sister named Penny.
When Melody starts fifth grade, her parents present her with an electric wheelchair, which gives Melody a sense of freedom she has never had before. Her school also starts an inclusion program to allow the H-5 students to interact with the other classes. During these classes, Melody meets a nice girl named Rose. Unfortunately, she also encounters two girls, Molly and Claire, who both have a reputation for being mean to almost everyone. Melody’s teacher, Mrs. Shannon, hires Catherine as an aide to help Melody in her classes. Melody and Catherine find a device called a Medi-Talker on the internet to help Melody communicate. Melody’s parents order it for her. The device provides a voice for her thoughts.
In Melody’s language arts class, her teacher, Miss Gordon, tells the students about an autobiography project they will be doing at the end of the year. Mr. Dimming, Melody’s history teacher, has the class participate in a practice exercise for their school’s Whiz Kids quiz team. Every year the school sends a team to the Whiz Kids competition. During the practice exercise, Melody achieves a perfect score. Her teacher and her classmates, particularly Molly and Claire, are shocked and skeptical. This skepticism bothers Melody but with the help of Catherine in school, and Mrs. V after school, she studies hard to properly prepare for the team tryouts. Melody takes the real test, getting another perfect score, and secures a place on the school team. Mr. Dimming apologizes to Melody for underestimating her. The quiz team spends the next two weeks studying and practicing after school. Even though Melody is part of the team, she does not feel a sense of belonging.
The Spaulding Street Elementary team competes in the southwest Ohio regional competition and wins. Melody receives an unwanted amount of media attention, which makes her team members jealous.
The Brooks family and Mrs. V take Melody and her mom to the airport so they can catch a plane headed to the Whiz Kids national finals in Washington, D.C. When they arrive at the airport, an airline employee informs them that their plane has been canceled due to bad weather. She tells them that the rest of the team arrived early and was able to board a different flight before the cancellations began. Melody is distraught that her team left her behind.
The next morning, Melody’s father comes into her room with the news that the team came in ninth place in the D.C. finals and won a tiny trophy. Melody decides she wants to go to school to show that she can rise above the whole situation and to see Catherine. It’s a very stormy day and due to the lightning, Melody is forced to use her manual wheelchair and her old Plexiglas communication board. With difficulty, her mother gets her into the car for school. Suddenly, Melody sees Penny run out of the house. Melody realizes her mother didn’t notice, so she starts frantically screaming and flailing about. Her mother, frustrated with Melody and the morning’s events, starts backing the car down the driveway, and they feel a soft thump. Horrified, they realize it was Penny. Penny has a badly broken leg and will undergo a surgical procedure, but she will be fine.
Melody goes to school to face her quiz team teammates. They all make excuses, even Mr. Dimming, as to why they didn’t call her and why they left her behind. The team wants to give Melody their little plastic trophy to make up for it. Melody starts giggling when suddenly her hand jerks, knocking the trophy to the ground and causing it to break. She uses her Medi-Talker to say that she doesn’t want it and they deserve it. Still laughing, she leaves the room.
At the end of fifth grade, Melody thinks that maybe she is not so different from everyone else after all. Perhaps she carries some of the same worries and attitudes as other fifth graders. She starts working on her autobiography for Miss Gordon’s class. She begins her autobiography titled Out of My Mind with "I'm surrounded by thousands of words," the exact same words that start the book.