Ramona is an energetic eight-year-old girl entering the third grade. She rides the bus alone for the first time and tries hard to act independent. Her family's current financial situation requires her to spend her afternoons at a neighbor's house, a responsibility she intensely dislikes but accepts as her contribution to the household.

Mr. Quimby is a father making a mid-life career change. He works part-time at a frozen food warehouse while taking college courses to become an art teacher. He attempts to keep his family's spirits high despite their tight budget, using humor and patience to manage the stress of his busy schedule.

Mrs. Quimby works full-time as a receptionist to support her family while her husband attends college. She manages the household chores and daily schedules, often feeling the physical strain of her heavy responsibilities. She expects her daughters to help out and behave, particularly regarding their after-school arrangements.

Beezus is Ramona's older sister, who is starting her first year at junior high. She is entering adolescence and occasionally clashes with her parents over rules and social expectations. Despite her desire for independence, she remains a responsible older sibling who understands the family's financial pressures.

Willa Jean is a four-year-old girl attending nursery school. She expects constant entertainment from older children, insisting that anyone visiting her house play elaborate games of dress-up. She relies on her grandmother to enforce her playtime rules and ensure she gets her way.

Danny is a spunky boy in Ramona's third-grade class who rides the same school bus. He tests boundaries early on by kicking seats and taking items that do not belong to him. He responds well to confidence and quickly develops a rapport with classmates who stand their ground.

Mrs. Whaley is the third-grade teacher at Cedarhurst Primary School. She introduces a relaxed learning environment, notably instituting a daily independent reading time. She speaks plainly to her students, though her casual remarks can sometimes be misinterpreted by young listeners.

Howie is a boy in Ramona's neighborhood who was once her closest companion. Now in a different class, he spends his afternoons riding bicycles with a new group of peers, physically distancing himself from his former friend.

Mrs. Kemp is a grandmother who provides after-school care for neighborhood children. She keeps a watchful eye over her home and expects older children to accommodate the playtime demands of her young granddaughter.

Mrs. Larson is the secretary at Cedarhurst Primary School. She manages the front office and provides practical care for students who encounter minor accidents or illnesses during the school day.

Sara is a third-grade student at Cedarhurst Primary School. She is a friendly classmate who participates in group activities and helps deliver messages between the classroom and absent peers.

Janet is a student in Mrs. Whaley's third-grade class. She acts as an active participant in classroom projects and collaborates easily with her peers on creative assignments.

Bruce is a young boy who visits the Kemp household for playdates. He frequently gets roped into participating in the imaginative dress-up games dictated by the younger children in the home.

Mary Jane is a middle school student who attends Rosemont Junior High. She hosts social gatherings and sleepovers that her friends are eager to attend.