Set in 1930s Edinburgh, The Prime of Miss Jean Brodie is the story of a charismatic schoolmistress and her influence on the pupils of the Marcia Blaine School for Girls. One group of girls in her junior class (Sandy, Rose, Monica, Jenny, Eunice and Mary) become known throughout the school as 'the Brodie set', and Miss Brodie herself calls them the crème de la crème. When the girls move on to the senior school, Miss Brodie retains her influence over them, and she takes steps to ensure her continued involvement in their lives.

Miss Brodie's teaching methods are flamboyant and unconventional. She shows an airy disregard for the formal curriculum, choosing to teach her class about Italian Renaissance Art, the virtues (as Miss Brodie sees it) of Mussolini's Fascist regime and her own love life at the expense of long division and the dates of famous Scottish battles. This cavalier and individualistic attitude brings her into conflict with the headmistress, Miss Mackay, who sets about searching for evidence that she may use to discredit Miss Brodie and force her dismissal.

It is in Miss Brodie's nature to sail close to the wind, and Miss Mackay is soon able to build her dossier. It gradually becomes evident to the Brodie set and to certain members of staff that Miss Brodie is romantically involved with Mr. Lowther, the singing master, and that she also carries a torch for Mr. Lloyd, the art master, a married man. Initially, the girls take a keen interest in these events as a means of discovering ‘the facts of life’. As they grow older they become more directly involved in Miss Brodie’s world and in her schemes. Through the machinations of their former teacher, some of the girls become models for Mr. Lloyd at his studio.

Miss Brodie plans to have Rose become the artist’s lover, so she can enjoy a vicarious fulfilment of her own desires. In the event it is the less beautiful Sandy who takes on that role. Astute, sensitive and intelligent, Sandy grows increasingly suspicious of Miss Brodie and resentful of her controlling nature. When one of the peripheral members of the Brodie set runs away to fight in the Spanish Civil War and is killed, Sandy becomes aware that this may be a direct consequence of Miss Brodie’s teachings on fascism, disastrously misunderstood by her ill-fated pupil. Sandy decides to reveal the details of Miss Brodie's fascist leanings and educational slant to the authorities. Miss Brodie is dismissed from her post.

A few years later, Jean Brodie is a broken, though still defiant, figure suffering from a terminal illness. She speculates endlessly as to which of her girls 'betrayed' her, though she never suspects Sandy. The influence of Miss Brodie ‘in her prime’ on the lives of her grown-up pupils is an enduring one. In Sandy's case, it determines the course of her life.