Ramona Quimby, an imaginative and free-spirited third-grader, often finds herself in hilarious predicaments both at school and at home, thanks in part to her mischievous neighbor and best friend, Howard Kemp. As her family's financial situation deteriorates after her father, Robert, unexpectedly loses his job, Ramona resorts to her creative ideas to make money. Unfortunately, her endeavors lead to a series of amusing blunders, such as persistently teasing her older sister, Beezus, especially in front of the dashing paperboy, Henry Huggins, who has captured Beezus' attention.
Meanwhile, Robert grapples with the challenge of pursuing a fulfilling career that aligns with his artistic ambitions, much to the chagrin of his wife, Dorothy. Amidst the family turmoil, Ramona's aunt Beatrice, who shares a name with her sister, emerges as a symbol of acceptance, celebrating Ramona's unique spirit.
However, a disastrous incident occurs when an old flame of Beezus, Hobart—who happens to be Howard's uncle—gets caught up in a painting accident, forcing Ramona to shelve her money-making schemes. In a moment of recklessness, she sabotages her school portrait by cracking a raw egg over her head and making an absurd face for the camera when asked to say “Peas” instead of “Cheese.” As her worries mount, she learns from her classmate Susan that her father has lost his job, which not only leads to his divorce but also his relocation to Tacoma, deeply affecting Ramona. The emotional toll even causes her to fall ill, prompting Robert to pull her out of school, disrupting an important job interview.
As discord brews at home, Ramona and Beezus attempt to prepare dinner for their parents, resulting in chaos when a pan ignites while Beezus is preoccupied on the phone with Henry. This escalating argument reveals Beezus's secret affection for him. Following this revelation, Ramona faces the heartbreaking loss of her beloved cat, Picky-Picky, leading to a touching funeral that serves as a moment of reconciliation for the sisters.
With a job opportunity in Oregon, Robert decides to sell their home, setting off a whirlwind of packing and preparations for the move. During an open house, Ramona accidentally initiates a water fight with the neighbors, unearthing forgotten memories from Beezus and Hobart's teenage romance. Their rekindled relationship reaches a climax when Hobart proposes to Beezus, who reluctantly agrees, thrusting the family into a flurry of wedding preparations.
As the weight of her aunt's betrayal bears down on her, Ramona (playing herself) seeks solace in the attic, only to have the fragile floorboards crumble beneath her. With her legs dangling precariously over the living room, the family eventually gathers as Robert (playing himself) reprimands her for her childishness, his words striking deep. Feeling lost and rejected, Ramona attempts to run away, but Dorothy's pleas to stay fall on deaf ears. However, as she leaves, Dorothy gives her a substantial suitcase meant to keep Ramona close. When the suitcase spills open at a bus stop, Ramona discovers a poignant surprise—a sketchbook filled with illustrations of her by Robert, symbolizing their artistic connection. Eventually, her family finds her, leading to a heartfelt reunion that fills the air with joy.
At Beezus and Hobart's wedding celebration, Ramona becomes the unlikely hero when she retrieves the lost wedding ring that Howard accidentally dropped. As the festivities continue, Beezus and Henry share a romantic dance, bravely taking a chance on love. Robert's fortunes also seem to improve when Mrs. Meachum's glowing reference earns him a new position as an art teacher at Ramona's school, much to her delight since it means they won't have to relocate and her parents are on the path toward mending their marriage. As Beezus and Hobart prepare for their first adventure as a married couple in Alaska, Ramona gifts her mother a cherished locket with her school picture, resulting in an emotional moment that earns Dorothy's proud declaration: “You're extraordinary.”
