Sam Gribley, an intelligent and determined boy in his early teens, is the main character in My Side of the Mountain. Having grown up in a family of eleven in New York City, he values his privacy and independence. His mother, who once worked as a dietician in a children's hospital, and his father, a former sailor who now works on the docks, are willing to let Sam try his hand at independent living.

Sam's closest companions in the woods are Frightful, a trained peregrine falcon; Jesse Coon James, a raccoon; and Baron Weasel. These animals become his friends, providing protection and serving as partners for conversation.

Sam goes to great lengths to avoid contact with other people during his year in the wilderness, but he does make several human friends. One is Miss Turner, a librarian who helps him locate the old farmstead and gives him a haircut with her library scissors. Another is Bando, a college English teacher who becomes lost in the mountains while hiking. Bando spends ten days with Sam in the summer and returns for a visit at Christmas; he makes and plays willow whistles, and fires clay containers for blueberry jam. A third friend is a boy who works in the drugstore, known to Sam as "Mr. Jacket." By the end of the year this youth, whose real name is Tom Sidler, is a regular weekend guest in the woods.

Other characters in the story are Bill, a kind old man who teaches Sam how to make a fire with flint and steel; ninetyseven- year-old Mrs. Thomas Fielder, who forces Sam to pick strawberries for her; the fire warden, who is puzzled by the sight of Sam's fires; deer poachers and other hunters; Aaron, a hiker from New York who comes to the Catskills over the Passover holidays; and Matt Spell, a young reporter from a New York newspaper who writes an article about Sam.

The book develops the theme of independence versus the need for relationships, examines the causes of loneliness, criticizes society's lack of respect for privacy, and questions whether people are "allowed to live in America today and be quietly different." The novel also emphasizes the possibility and joy of living close to nature. Sam's daily actions are creative and ingenious; he tackles everyday problems with common sense and determination.