The main character, Leigh Marcus Botts, introduces us to the people in Dear Mr. Henshaw through letters he writes to children's author Boyd Henshaw and later in his diary. Leigh describes himself as "just a plain boy...the mediumest boy in the class." Although the school doesn't label him as "Gifted and Talented," he insists he's "not stupid either." Intelligent, sensitive, thoughtful, and somewhat of a loner, Leigh considers himself "just a boy nobody pays much attention to." The author, Henshaw, is depicted through Leigh's reactions to his letters. Frustrated by frequent inquiries from students, Henshaw sometimes gives silly answers to Leigh's questions and poses some of his own. When Leigh responds, Henshaw shows genuine concern for the troubled boy, trying to help despite his busy schedule. Leigh never gets to meet Henshaw, but near the book's end, he encounters a "Famous Author" who describes Boyd Henshaw as "a very nice young man with a wicked twinkle in his eye."

Other characters featured in the letters and diary include Leigh's father, Bill Botts, a truck driver who, despite his positive traits, often breaks promises and hasn't fully matured; his mother, Bonnie Botts, a single parent working for a caterer while studying to become a nurse; his dog, Bandit, who travels with Leigh's father; the custodian, Mr. Fridley, a "nice, sort of baggy and comfortable" man whom Leigh prefers over his teacher; Miss Martinez, Leigh's sixth-grade teacher; the school librarian, Miss Neely, who surprises Leigh by noticing him; Chuck, a man working at the neighboring gas station; Barry, a friend Leigh meets at school; and Angela Badger, the Famous Author.

Besides Mr. Henshaw, another character Leigh never meets but mentions in his writing is significant. While speaking to his father on the phone, Leigh hears a child's voice in the background asking Bill Botts when they are going out for pizza. This "pizza boy" symbolizes a new child in Leigh's father's life, stirring feelings of hurt and jealousy in Leigh. The array of characters provides a complete picture of Leigh's life, as illustrated through his interactions in his writing.

The theme of growing up is woven throughout the entirety of the book. Leigh's initial letters to Mr. Henshaw are youthful, filled with charming language and innocent errors typical of young children. As Leigh matures, even just from fall to spring during his sixth-grade year, his grasp of writing improves. His comprehension of life's complexities, emotions, and people also deepens. At the start of the book, Leigh describes his father as "real big" and clearly takes pride in his father's large truck. However, he gradually understands that, despite his father's good traits, he is unreliable and not trustworthy. Nevertheless, Leigh learns to love his father, accepting his flaws. By the book's conclusion, Leigh has matured, possibly surpassing his father in maturity. Bill Botts proudly acknowledges to his son, "You're smarter than your old man."

Leigh's growth can be partly attributed to his mother and, indirectly, to Mr. Henshaw. Leigh is impressed by Mr. Henshaw's books, and the author's responses to Leigh's writing questions, along with his own list of questions, compel Leigh to focus on writing techniques. Leigh's wise mother insists he answer these questions and chooses not to fix the television so he uses his mind more. She also prevents him from "hanging around" the gas station or other places. His mother's encouragement and Mr. Henshaw's suggestion to keep a journal provide the motivation Leigh needs to develop his writing skills and aspire to be a "famous book writer with a beard like [Mr. Henshaw]." Leigh matures, not only as a son who learns to accept and love his father but also as a budding writer who eventually receives honorable mention in his school's "Young Writer's Workbook."