The following version of the book was used to create this study guide: Harrigan, Stephen. The Leopard Is Loose. Penguin Random House, New York, NY. 2022. Kindle AZW file.

The novel opens with Grady explaining that the Oklahoma Historical Society asked him to record his memories of the days after a leopard escaped from the zoo in Oklahoma City. Grady tried to record those memories, as requested. When he cannot organize his thoughts, he sets out to write them as a story instead.

Five-year-old Grady lives a sheltered life with his brother Danny, who is a year older, and his mother Bethie. Grady's father Burt had died in a military accident shortly after World War II. The story is set in the early 1950s. Grady's family lives in an apartment built by his grandparents, Big Dan and Babi. The apartment is just across the yard from their family home. Grady's uncles, Emmett and Frank, live in the second story of Grady's apartment. Emmett and Frank were both on active duty during the war. Vivian, Bethie's sister, lives in the main house with Babi and Big Dan. The extended family takes care of Grady and Danny while Bethie works as a nurse. Frank and Emmett play an important role in this. They usually spend Sunday afternoons with Grady and Danny, often making trips to the zoo. One Sunday shortly before the leopard's escape, Grady and Danny are perched on the fence around the leopard enclosure when the leopard makes a leap for the fence. Frank and Emmett each grab a boy though the leopard's leap is short of the fence. This is an example of the protective nature of this relationship.

A short time later, the leopard successfully escapes. The city goes into a panic over the escaped leopard with many predicting the cat would attack humans without provocation. Many go hunting the leopard without any idea where to look. Danny and Grady become more carefully protected, but their lives continue much as usual. They sometimes go with Big Dan to his car dealership. One day, Grady hears Big Dan put a stop to a white man harassing a Black girl who is waiting for sandwiches at a lunch counter. Another day, the boys are caught up in a fight as a Black man wants admittance to a museum on a Sunday afternoon. The relationship between Bethie and her brothers becomes strained as they struggle with their own problems, including barely-controlled tempers and too much alcohol.

Meanwhile, Bethie is beginning a relationship with a man named Hugh, and it seems their relationship is becoming serious. Bethie worries about moving the boys to Texas, away from the family that has played such an important role in their lives. Frank and Emmett are riding around with Grady and Danny one day when they believe they see the leopard. Emmett shoots it only to learn it is a dog, the beloved pet of a Black family. The men of that community confront Emmett and Frank, and it turns into a fight with most of the Blacks arrested. Emmett and Frank wind up arrested as well, just as Bethie arrives and retrieves the boys. Grady has an emotional meltdown, prompting Bethie and Hugh to stop on the side of the road. Bethie comforts the boys until they are calmer, and Grady is the first to spot the leopard. It has eaten meat dosed with a sedative, but the dose was too high and the cat is dying. Bethie and the boys rub the animal to soothe him, and a photographer captures an image of the boys petting the cat. A short time later, Bethie marries Hugh and the boys say good-bye to their grandparents, aunt, and uncles.