The Charterhouse of Parma chronicles the adventures of the young Italian nobleman Fabrice del Dongo from his birth in 1798 to his death. Fabrice spends his early years in his family's castle on Lake Como, while most of the rest of the novel is set in a fictionalized Parma (both locations are in modern-day Italy).

The book begins with the French army sweeping into Milan and stirring up the sleepy region of Lombardy, which was allied with Austria. Fabrice grows up surrounded by intrigues and alliances for and against the French — his father the Marchese comically fancies himself a spy for the Viennese. It is broadly hinted at that Fabrice may have actually been fathered by a visiting French lieutenant. The novel's early section describes Fabrice's rather quixotic effort to join Napoleon when the latter returns to France in March 1815 (the Hundred Days). Fabrice at seventeen is idealistic, rather naive, and speaks poor French. However, he will not be stopped and leaves his home on Lake Como to travel north with false papers. He wanders through France, losing money and horses rapidly. He is imprisoned as a spy, but escapes with the aid of the jailer's wife who develops a fondness towards Fabrice, donning the uniform of a dead French hussar. In his excitement to play the role of a French soldier, he wanders onto the field at the Battle of Waterloo.