Beezus is a sensible nine-year-old girl who often feels responsible for supervising her mischievous four-year-old sister, Ramona. She admires her Aunt Beatrice and strives to be well-mannered and rule-oriented. These traits often put her at odds with Ramona's noisy, chaotic behavior. Beezus worries about typical pre-adolescent concerns, such as seeking adult approval from her art teacher and managing the guilt she feels when she becomes angry with her sibling.

Ramona is Beezus's headstrong, highly imaginative four-year-old sister. She views the world with pure curiosity and operates with a unique logic that confuses her family. She rides her tricycle indoors, pretends to have an invisible lizard named Ralph, and throws sudden tantrums when her plans fail. She acts as a loud, disruptive force in the Quimby household, whether she is taking a single bite out of every apple in the basement or organizing an impromptu party for the neighborhood.

Aunt Beatrice is Dorothy's sister and Beezus's namesake. She works as a fourth-grade teacher, drives a yellow convertible, and lives in an apartment building. She brings a sense of calm and perspective to the Quimby household, arriving with thoughtful gifts and a store-bought cake to rescue Beezus's birthday celebration. She offers comfort by sharing humorous stories from her own childhood.

Dorothy is the mother of Beezus and Ramona. She is a homemaker who spends her days running the household, cooking meals, and supervising her daughters' frequent conflicts. She works hard to maintain peace in her home while raising two very different children. She comforts her oldest daughter by sharing vulnerable memories of her own youthful arguments with her sister.

Mr. Quimby is the father of Beezus and Ramona. He works during the day and expects a quiet house upon his return, occasionally issuing strict rules like banning a noisy book. He generally sits behind his daily newspaper, leaving the immediate discipline of the children to his wife.

Henry is a neighborhood boy who values Beezus's intelligence and enjoys spending time with her. He frequently visits the Quimby house to play checkers, bringing along his dog, Ribsy. His visits offer Beezus a welcome break from her sisterly duties, though their quiet games are usually interrupted by Ramona's loud antics.

Ribsy is Henry Huggins's pet dog. He is a cautious animal who closely watches the erratic behavior of the Quimby children. He unwittingly becomes a participant in Ramona's mischief when he attempts to eat her cookie and gets locked inside a bathroom as punishment.

Howie is a nursery school classmate of Ramona. He shares her loud, energetic approach to play. He frequently visits the Quimby household and gleefully leads an indoor parade with a vacuum cleaner and improvised instruments during Ramona's unplanned party.

Willa Jean is Howie's toddler sister. She tags along with her older brother during playdates at the Quimby house, adding another layer of noise and potential messes for Mrs. Quimby and Beezus to supervise.

Mrs. Kemp is a neighborhood mother whose children attend the same nursery school as Ramona. She calls the Quimby house to coordinate social visits for Howie and Willa Jean, unaware of the stress these energetic playdates cause for the older members of the household.

Miss Robbins leads Beezus's Friday after-school art class at the local recreation center. She is an encouraging teacher who praises Ramona's uninhibited drawings of invisible lizard tracks. She later helps Beezus overcome her anxiety, pushing her to create a whimsical painting of a cotton-candy-breathing dragon.

Wayne is a disruptive boy in Beezus's Friday art class. He sucks on a grape lollipop and teases Beezus about her paintings. He causes a massive paint spill on the classroom floor during a physical scuffle with Ramona over his candy.

Miss Evans is the local librarian. She calmly processes a damaged book return after Ramona scribbles her name in purple crayon on every page. She firmly enforces the library rules while understanding the challenging dynamic between the young siblings.

Mrs. Wisser is a neighbor of the Quimby family. She encounters the girls on their way to the library and finds Ramona's paper rabbit ears endearing. Her praise of the four-year-old frequently causes Beezus to feel self-conscious and jealous.